DIPHTHERIA,

PERTUSSIS &
TETANUS
Dr Sarika Gupta, Asst. Professor

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, nonspore-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 130g/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: bullneck 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)

1.
2.
3.
4.
5.
6.

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:
Common cold
Congenital syphilis snuffle
Sinusitis
Adenoiditis and foreign body in nose
Streptococcal pharyngitis
Infectious mononucleosis

COMPLICATIONS
1.

2.

Respiratory tract obstruction by pseudomembranes:

bronchoscopy or intubation and mechanical ventilation
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 20,000120,000 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

PERTUSSIS (WHOOPING COUGH)

Cough of 100 days

Whooping cough: whooping sound made when

gasping for air after a fit of coughing

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.

2.

3.

Secondary pneumonia (1 in 5) and apneic spells (50%;

neonates and infant<6 months of age)
Neurological complications: seizures (1 in 100) and
encephalopathy (1 in 300) due to the toxin or hypoxia or
cerebral hemorrhage
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.

2.

3.

Suspected on the basis of history and clinical examination

and is confirmed by culture, genomics or serology
Elevated WBC count with lymphocytosis. The absolute
lymphocyte count of 20,000 is highly suggestive
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

4.

5.

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.
PCR: most sensitive to diagnose; can be done even after
antibiotic exposure. It should always be used in addition with
cultures
Direct fluorescent antibody testing: low sensitivity and
variable specifity

TREATMENT
1.

2.

3.

Avoidance of irritants, smoke, noise and other cough

promoting factors
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
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

LOCKJAW

Tetanus

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

1.

2.

Best in the ICU as child may need early and aggressive

airway management
The goals of treatment include
Halting toxin production
Wound debridement
Antimicrobial therapy: metronidazole or penicillin G for 710 days
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.

4.

5.

Control of muscle spasms

Avoidance of sensory stimuli
Sedatives: diazepam
Management of autonomic dysfunction:
Magnesium sulfate, beta blockers, morphine sulfate
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