Diphtheria, Pertusis & tetanus

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Transcript Diphtheria, Pertusis & tetanus

DIPHTHERIA,
PERTUSSIS &
TETANUS
Dr Sarika Gupta, Asst. Professor
Bull-neck appearance of diphtheritic cervical
lymphadenopathy
Diphtheria (Corynebacterium diphtheriae)
Diphtherais Greek word for leather
INTRODUCTION
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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
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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
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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
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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
Entry into nose or mouth
The organism remains in the superficial layers of skin lesions or respiratory tract
mucosa, inducing local inflammatory reaction
The major virulence of the organism lies in its ability to produce the
potent 62-kd polypeptide exotoxin, which inhibits protein synthesis and
causes local tissue necrosis
Within the first few days of respiratory tract infection , a dense necrotic
coagulum of organisms, epithelial cells, fibrin, leukocytes and erythrocytes
forms, advances, and becomes a gray-brown, leather-like
adherent pseudomembrane . Removal is difficult and reveals a bleeding
edematous submucosa
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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
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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
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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
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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
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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
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Clinical features
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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
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Elek test: rapid diagnosis (16-24 hrs)
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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
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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
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Toxic Neuropathy:
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Acutely or 2-3 wk after: hypoesthesia and soft palate paralysis
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Afterwards weakness of the posterior pharyngeal, laryngeal, and facial
nerves : a nasal quality in the voice, difficulty in swallowing and risk for
aspiration
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Cranial neuropathies (5th wk): oculomotor and ciliary paralysisstrabismus, blurred vision, or difficulty with accommodation
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Symmetric polyneuropathy (10 days to 3 mo): motor deficits with
diminished deep tendon reflexes
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Monitoring for paralysis of the diaphragm muscle
Recovery from the neuritis is often slow but usually
complete. Corticosteroids are not recommended.
TREATMENT
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Antitoxin:
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Mainstay of therapy
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Neutralizes only free toxin, efficacy diminishes with elapsed time
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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
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Antimicrobial therapy
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Halt toxin production, treat localized infection and prevent transmission
of the organism to contacts
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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
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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:
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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)
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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:
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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
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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
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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
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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
The organism get attached to the respiratory cilia and toxin causes
paralysis of cilia
muocopurulent-sanguineous exudate forms in the respiratory tract
-This exudate predisposes to atelectasis, cough, cyanosis and pneumonia
-Organism causes local tissue damage and systemic effects mediated
through its toxin
CLINICAL MANIFESTATIONS
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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
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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
Secondary pneumonia (1 in 5) and apneic spells (50%;
neonates and infant<6 months of age)
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Neurological complications: seizures (1 in 100) and
encephalopathy (1 in 300) due to the toxin or hypoxia or
cerebral hemorrhage
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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
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DIAGNOSIS
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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
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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
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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
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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
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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
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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
Tetanus occurs when spores of C.tetani found in soil gain access to
damaged human tissue
After inoculation, C. tetani transforms into a vegetative rod shaped
bacterium and produces the metalloprotease, tetanospasmin
After reaching the spinal cord and brainstem via retrograde axonal
transport and binding tightly and irreversibly to receptor , tetanus toxin
blocks neurotransmission
Net effect is disinhibition of anterior horn cells and autonomic nervous
system resulting in increased muscle tone, painful spasms and
widespread autonomic instability
PREDISPOSING FACTORS
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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
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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
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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
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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
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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
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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