Diphtheria, Pertussis

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Diphtheria, Pertussis tetanus

• Dr Sarika Gupta, Asst. Professor

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Bull-neck appearance of diphtheritic
cervical lymphadenopathy

• Diphtheria (Corynebacterium diphtheriae)
• Diphtherais
  Greek word for leather

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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

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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

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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

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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

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PATHOGENESIS
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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
• Myocarditis10-14 days
• Demyelination of nerves 3-7 weeks

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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

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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

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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 bull-neck 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

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• 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)

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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

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COMPLICATIONS

• 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
• 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.

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TREATMENT

• 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
• 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

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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

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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 lt30 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
• SameRepeat 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

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Cough of 100 days
PERTUSSIS (WHOOPING COUGH)

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

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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)

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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

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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

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PATHOGENESIS
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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

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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 coughgt2 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

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COMPLICATIONS

• Secondary pneumonia (1 in 5) and apneic spells
  (50 neonates and infantlt6 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

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DIAGNOSIS

• 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

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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.
• 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

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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 childrenlt6
   months and for childrengt6 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)

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PREVENTION

• All household contacts should be given
  erythromycin for 2 weeks
• Children lt7 years of age not completed the four
  primary dose should complete the same at the
  earliest
• Children lt7 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

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LOCKJAW

• Tetanus

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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

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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

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PATHOGENESIS
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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

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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

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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

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TREATMENT

• 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 7-10 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.

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TREATMENT

• 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

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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

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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