Pertussis

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Pertussis

• Dr. Rezai MS
• Pediatrics infectious disease sub specialist

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ETIOLOY

• Bordetella pertussis
• Bordetella parapertussis is an occasional cause
• Exclusive pathogens of humans and some primates.
• B. bronchiseptica is a common animal pathogen.

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Protracted coughing

• Mycoplasma
• Parainfluenza or influenza viruses
• Enteroviruses
• Respiratory syncytial virus
• Adenoviruses.

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EPIDEMIOLOY

• 60 million cases of pertussis each year
• gt500,000 deaths.
• Widespread use of pertussis vaccine led to a gt99
  decline in cases.
• Pertussis is increasingly endemic.

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EPIDEMIOLOY

• Approximately 60 of cases are in adolescents and
  adults.
• Infants have the highest morbidity
• Pertussis is extremely contagious
• attack rates as high as 100

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EPIDEMIOLOY

• Chronic carriage by humans is not documented.
• After intense exposure as in households, the rate
  of subclinical infection is as high as 80 in
  fully immunized or previously infected
  individuals.

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EPIDEMIOLOY

• Neither natural disease nor vaccination provides
  complete or lifelong immunity against reinfection
  or disease.
• Protection against typical disease
• wane 3-5 yr after vaccination
• unmeasurable after 12 yr

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PATHOGENES

• B.ordetella organisms are tiny, fastidious,
  gramnegative coccobacilli that only colonize
  ciliated epithelium.
• Only B. pertussis expresses pertussis toxin (PT),
  the major virulence protein.
• (PT), histamine sensitivity, insulin secretion,
  leukocyte dysfunction

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PATHOGENES

• PT causes lymphocytosis immediately
• Tracheal cytotoxin, adenylate cyclase, and PT
  appear to inhibit clearance of organisms.
• Tracheal cytotoxin, dermonecrotic factor, and
  adenylate cyclase are postulated to be
  predominantly responsible for the local
  epithelial damage that produces respiratory
  symptoms and facilitates absorption of PT.

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CLINICAL MANIFESTATION

• 3stages
• Catarrhal
• paroxysmal
• convalescent

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CLINICAL MANIFESTATION

• incubation period ranging from 3-12 days
• catarrhal stage (1-2 wk) begins insidiously
  congestion and rhinorrhea, lacrimation
• low-grade fever
• sneezing
• conjunctival suffusion

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CLINICAL MANIFESTATION

• paroxysmal stage (2-6 wk).
• The cough begins as a dry, intermittent,
  irritative hack and evolves into the inexorable
  paroxysms that are the hallmark of pertussis.
• anxious aura, whoop follows after caugh
• Post-tussive emesis is common

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CLINICAL MANIFESTATION

• At the peak of the paroxysmal stage, patients may
  have more than 1 episode hourly.

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CLINICAL MANIFESTATION

• Convalescent stage (2 wk)
• The number, severity, and duration of episodes
  diminish.

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CLINICAL MANIFESTATION

• Infants lt3 mo of age
• Do not display classical stages.
• Cough (expiratory grunt) may not be prominent.
• Whoop infrequently occurs in infants lt3 mo
• Cyanosis can follow a coughing paroxysm
• Apnea may be the only symptom.
• Apnea can occur without a cough

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CLINICAL MANIFESTATION

• Paradoxically, in infants, cough and whooping may
  become louder and more classic in convalescence.
• Convalescence includes intermittent paroxysmal
  coughing throughout the 1st year of life,
  including "exacerbations" with subsequent
  respiratory illnesses these are not due to
  recurrent infection or reactivation of
  B.pertussis.

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CLINICAL MANIFESTATION

• Immunized children have foreshortening of all
  stages of pertussis.
• Signs of lower respiratory tract disease are not
  expected unless complicating secondary bacterial
  pneumonia is present.
• Conjunctival hemorrhages and petechiae on the
  upper body are common.

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DIAGNOSIS

• Clinical suspect
• Leukocytosis (15,000-100,000 cells/mm3) due to
  absolute lymphocytosis is characteristic in the
  catarrhal stage.
• Lymphocytes are of T- and B-cell origin and are
  normal small cells, rather than the large
  atypical lymphocytes seen with viral infections.

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DIAGNOSIS

• Eosinophilia is not a manifestation of pertussis.
• A severe course and death are correlated with
  extreme leukocytosis (median peak white blood
  cell count fatal vs nonfatal cases, 94 vs 18 x
  109 cells/L) and thrombocytosis (median peak
  platelet count fatal vs nonfatal cases, 782 vs
  556 x 109/L)

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DIAGNOSIS

• Mild hyperinsulinemia and reduced glycemic
  response to epinephrine
• Hypoglycemia is reported only occasionally.
• Parenchymal consolidation suggests secondary
  bacterial infection.
• Pneumothorax, pneumomediastinum, and air in soft
  tissues can be seen occasionally.

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DIAGNOSIS

• Isolation of B. pertussis in culture remains the
  gold standard for diagnosis.
• deep nasopharyngeal aspiration or by use of a
  flexible swab, preferably a dacron or calcium
  alginate swab, held in the posterior nasopharynx
  for 15-30 sec (or until coughing).

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• A 1.0 casamino acid liquid is acceptable for
  holding a specimen up to 2 hr Stainer-Scholte
  broth or Regan-Lowe semisolid transport medium is
  used for longer periods, up to 4 days.

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• Direct testing of nasopharyngeal secretions by
  DFA is a rapid test
• PCR to test nasopharyngeal wash specimens
• Less than 10 of any of these test results are
  positive in partially or remotely immunized
  individuals tested in the paroxysmal stage.

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DIAGNOSIS

• Serologic tests in acute and convalescent samples
  are the most sensitive tests in immunized
  individuals and are useful epidemiologically.
• (lgG) antibody to pertussis toxin elevated gt2
  standard deviations above the mean of the
  immunized population indicates recent infection.

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DIAGNOSIS

• IgA and IgM pertussis antibody tests are not
  reliable methods for diagnosis.

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DIAGNOSIS

• Adenoviral infections are usually distinguishable
  by associated features, such as fever, sore
  throat, and conjunctivitis.
• Mycoplasma and B. pertussis in young adults can
  be difficult to distinguish on clinical grounds.

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DIAGNOSIS

• Chlamydia trachomatis
• B. pertussis is not associated with staccato
  cough (breath with every cough), purulent
  conjunctivitis, tachypnea, rales or wheezes

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TREATMEN

• Goals of therapy are to limit the number of
  paroxysms,to observe the severity of the cough,
  to provide assistance when necessary
• Infants lt3 mo of age are admitted to hospital
  almost without exception
• 3-6 mo unless witnessed paroxysms are not severe,
  and those of any age if significant complications
  occur.

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Typical paroxysms that are not life threatening

• Duration lt45 sec
• Red but not blue color change
• Tachycardia, bradycardia (not lt60 beats/min in
  infants)
• Oxygen desaturation that spontaneously resolves
  at the end of the paroxysm
• Whooping or strength for self-rescue at the end
  of paroxysm
• self-expectorated mucus plug
• post-tussive exhaustion but not unresponsiveness.

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TREATMEN

• Mist by tent can be useful in some infants with
  thick, tenacious secretions and excessively
  irritable airways.
• Large volume feedings are avoided.
• Portable oxygen, monitoring, or suction apparatus
  should not be needed at home.

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Hospital discharge

• If over a 48-hr period disease severity is
  unchanged or diminished
• No intervention is required during paroxysms,
• Nutrition is adequate, no complication has
  occurred
• Parents are adequately prepared for care at home.

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Antibiotics

• given when pertussis is suspected or confirmed
  primarily to limit the spread of infection and
  secondarily for possible clinical benefit.
• A 7- to 10-fold relative risk for infantile
  hypertrophic pyloric stenosis (IHPS) has been
  reported in neonates treated with orally
  administered erythromycin.
• Azithromycin is the preferred agent for use in
  neonates.

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Antibiotics
35
Antibiotics
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Adjunct Therapies

• Corticosteroids clinical use is not warranted.
• Beneficial effect of beta2-adrenergic is not
  documented

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Isolation

• Respiratory isolation with use of masks by all
  health care personnel entering the room.
• Children and staff with pertussis in child-care
  facilities or schools should be excluded until
  macrolide prophylaxis has been taken for 5 days.

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Care of Household and Other Close Contacts.

• A macrolide agent should be given promptly to all
  household contacts and other close contacts, such
  as those in daycare, regardless of age, history
  of immunization, or symptoms
• Children lt7 yr of age who received a 3rd dose gt6
  mo before exposure or a 4th dose 3 yr before
  exposure should receive a booster dose.

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Care of Household and Other Close Contacts

• Individuals 9 yr should be given a booster if
  they have not previously received Tdap and gt2 yr
  have passed since receipt of a diphtheria
  containing vaccine
• Coughing health care workers, with or without
  known exposure to pertussis, should be promptly
  evaluated for pertussis

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COMPLICATION

• Infants lt6 mo of age have excessive mortality and
  morbidity
• Infants lt4 mo of age account for 90 of cases of
  fatal pertussis.
• Preterm birth and young maternal age are
  significantly associated with fatal pertussis.

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COMPLICATION

• Progressive pulmonary hypertension or hemorrhage
  (especially in very young infants) and secondary
  bacterial pneumonia are usual causes of death.
  mortality rate of gt80.
• otitis media
• pneumonia(S. aureus, S. pneumoniae)
• Seizure

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COMPLICATION

• Seizures are usually a result of hypoxemia, but
  hyponatremia from excessive secretion of
  antidiuretic hormone during pneumonia can occur.
• infants with apnea raises the possibility of a
  primary effect of PT on the CNS.

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COMPLICATION

• Conjunctival and scleral hemorrhages petechiae on
  the upper body, epistaxis
• Hemorrhage in the central nervous system (CNS)
  and retina
• Pneumothorax and subcutaneous emphysema, and
  umbilical
• Inguinal hernias.

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COMPLICATION

• Children 2 yr may have abnormal pulmonary
  function into adulthood.
• Laceration of the lingual frenulum is not
  uncommon.

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PREVENTION

• 2, 4, and 6 mo of age.
• Booster15-18 mo, 4-6 yr
• A 5th dose is not necessary if the 4th dose in
  the series is administered on or after the 4th
  birthday.
• The preferred age for Tdap vaccination is 11-12
  yr

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Tetanus
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Tetanus(Clostridium tetani) lockjaw

• C. tetani is not a tissue-invasive organism and
  instead causes illness through the effects of a
  single toxin, tetanospasmin
• The human lethal dose of tetanus toxin is
  estimated to be 10-5 mg/kg.

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EPIDEMIOLOG

• Tetanus occurs worldwide and is endemic in
  approximately 90 developing countries.
• The most common form, neonatal (or umbilical)
  tetanus, kills approximately 500,000 infants each
  year, with about 80 of deaths in just 12
  tropical Asian and African countries.
• It occurs because the mother was not immunized.

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• maternal tetanus that results from postpartum,
  postabortal, or postsurgical wound infection with
  C.tetani.
• Most non-neonatal cases of tetanus are associated
  with a traumatic injury, often a penetrating
  wound inflicted by a dirty object such as a nail,
  splinter, fragment of glass, or unsterile
  injection.
• Tetanus occurring after illicit drug injection is
  becoming more common. (quinine)

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PATHOGENESIS

• Toxin is released after vegetative bacterial cell
  death and lysis.
• Tetanus toxin binds at the neuromuscular junction
  and enters the motor nerve by endocytosis, after
  which it undergoes retrograde axonal transport to
  the cytoplasm of the a motoneuron.

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PATHOGENESIS

• The autonomic nervous system is also rendered
  unstable in tetanus.
• C. tetani is not an invasive organism, its toxin
  producing vegetative cells remain where
  introduced into the wound.

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CLINICAL MANIFESTATION

• Generalized,which is more common
• Localized
• The incubation period typically is 2-14 days,
  but it may be as long as months after the injury.

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• In generalized tetanus
• About half of cases is trismus (masseter muscle
  spasm, or lockjaw).
• Headache, restlessness, and irritability are
  early symptoms, often followed by stiffness,
  difficulty chewing, dysphagia, and neck muscle
  spasm.
• The so-called sardonic smile of tetanus (risus
  sardonicus) results from intractable spasms of
  facial and buccal muscles.

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• Opisthotonos
• Laryngeal and respiratory muscle spasm can lead
  to airway obstruction and asphyxiation.
• Because tetanus toxin does not affect sensory
  nerves or cortical function, the patient
  unfortunately remains conscious, in extreme pain,
  and in fearful anticipation of the next tetanic
  seizure.

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• These seizures are characterized by sudden,
  severe tonic contractions of the muscles, with
  fist clenching, flexion, and adduction of the
  arms and hyperextension of the legs.
• Without treatment, the seizures range from a few
  seconds to a few minutes in length with
  intervening respite periods, but as the illness
  progresses, the spasms become sustained and
  exhausting.

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• The smallest disturbance by sight, sound, or
  touch may trigger a tetanic spasm.
• Dysuria and urinary retention result from bladder
  sphincter spasm forced defecation may occur.
• Fever, occasionally as high as 40C
• Notable autonomic effects include tachycardia,
  dysrhythmias, labile hypertension, diaphoresis,
  and cutaneous vasoconstriction.

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• The tetanic paralysis usually becomes more severe
  in the 1st wk after onset, stabilizes in the 2nd
  wk, and ameliorates gradually over the ensuing
  1-4 wk

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Neonatal tetanus (tetanus neonatorum)

• The infantile form of generalized tetanus,
  typically manifests within 3-12 days of birth
• As progressive difficulty in feeding (sucking and
  swallowing),associated hunger, and crying.
• Paralysis or diminished movement

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gt270,000 cases worldwide per year
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• stiffness and rigidity to the touch, and spasms,
  with or without opisthotonos, are characteristic.
  
• The umbilical stump may hold remnants of dirt,
  dung, clotted blood, or serum, or it may appear
  relatively benign.

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• Localized tetanus results in painful spasms of
  the muscles adjacent to the wound site and may
  precede generalized tetanus.

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Cephalic tetanus

• Rare
• bulbar musculature that occurs with wounds or
  foreign bodies in the head, nostrils, or face
• It also occurs in association with chronic otitis
  media.
• Cephalic tetanus is characterized by retracted
  eyelids, deviated gaze, trismus, risus
  sardonicus, and spastic paralysis of the tongue
  and pharyngeal musculature.

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DIAGNOSIS

• D iagnosis may be established clinically
• Who was injured or born within the preceding 2
  wk, who presents with trismus, other rigid
  muscles, and a clear sensorium.
• Routine laboratory studies are usually normal.

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• A peripheral leukocytosis may result from a
  secondary bacterial infection
• The cerebrospinal fluid is normal, although the
  intense muscle contractions may raise
  intracranial pressure.
• Neither the electroencephalogram nor the
  electromyogram shows a characteristic pattern.
• C. tetan is not always visible on Gram stain of
  wound material, and it is isolated in only about
  1/3 of cases

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DIFFERENTIAL DIAGNOSIS

• Trismus may result from para pharyngeal,
  retropharyngeal, or dental abscesses,or rarely,
  from acute encephalitis involving the brainstem.
• Rabies may be distinguished from tetanus by
  hydrophobia, marked dysphagia predominantly
  clonic seizures, and pleocytosis

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• Strychnine poisoning seldom produces trismus,
  and unlike tetanus, general relaxation usually
  occurs between spasms
• Hypocalcemia trismus is absent.
• epileptic seizures
• narcotic withdrawal

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TREATMENT

• Surgical wound excision and debridement
• Surgery should be performed promptly after
  administration of human tetanus immunoglobulin
  (TIG) and antibiotics.
• Excision of the umbilical stump in neonatal
  tetanus is no longer recommended.

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• Tetanus toxin cannot be neutralized by TlG after
  it has begun its axonal ascent to the spinal cord
• A single intramuscular injection of 500 U of TIG
  is sufficient
• Infiltration of TIG into the wound is now
  considered unnecessary.
• IVIG contains 4-90 U/mL of TIG

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• The human-derived immunoglobulins are much
  preferred because of their longer half-life (30
  days) and the virtual absence of allergic and
  serum sickness adverse effects.
• Intrathecal TIG, given to neutralize tetanus
  toxin in the spinal cord, is not effective.
• Penicillin G (100,000 U/kg/day divided every 4-6
  hr IV for 10-14 days) remains the antibiotic of
  choice

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• Metronidazole (500 mg every 8 hr IV for adults)
  appears to be equally effective.
• Erythromycin and tetracycline (for persons gt8 yr
  of age) are alternatives for penicillin-allergic
  patients.
• All patients with generalized tetanus need muscle
  relaxants.

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• Diazepam provides both relaxation and seizure
  control.
• The initial dose of 0.1-0.2/kg every 3-6 hr given
  intravenously is subsequently titrated to control
  the tetanic spasms, after which it is sustained
  for 2-6 wk before its tapered withdrawal.
• Magnesium sulfate, other benzodiazepines
  (midazolam), chlorpromazine, dantrolene, and
  baclofen are also used.

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• B aclofen should be used only in an intensive
  care unit setting.
• The highest survival rates in generalized tetanus
  are achieved with neuromuscular blocking agents
  such as vecuronium and pancuronium
• Autonomic instability is regulated with standard
  a and ß or (both) blocking agents morphine has
  also proved useful.

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SUPPORTIVE CARE

• Protected from all unnecessary sounds, sights and
  touch
• Prophylactic subcutaneous heparin may be of value
• Endotracheal intubation may not be required, but
  it should be done to prevent aspiration of
  secretions before laryngospasm develops.
• Early tracheostomy should be considered in severe
  cases not managed by pharmacologically induced
  flaccid paralysis.

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COMPLICATION

• Aspiration of secretions and pneumonia
• Pneumothorax and mediastinal emphysema.
• Rhabdomyolysis, renal failure
• long bone or spinal fractures
• Venous thrombosis, pulmonary embolism, gastric
  ulceration

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• Cardiac arrhythmias
• Unstable blood pressure
• labile temperature regulation

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PROGNOSIS

• Mortality is highest in the very young and the
  very old.
• An unfavorable prognosis
• lt7 days between the injury and the onset of
  trismus
• lt3 days between trismus and the onset of
  generalized tetanic spasms

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• A favorable prognosis
• long incubation period
• Absence of fever
• localized disease.
• Most fatalities occur within the 1st wk of
  illness.
• fatality rates for generalized tetanus are 5-35,
  and for neonatal tetanus extend from lt10 with
  intensive care treatment to gt75 without it.
• Cephalic tetanus has an especially poor prognosis
  because of breathing and feeding difficulties

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PREVENTION

• Antibody titer of 0.01 U/mL is considered
  protective.
• Vaccinaion2, 4, and 6 mo of age, with a booster
  at 4-6 yr of age and at 10 yr intervals
  thereafter throughout adult life (Td or Tdap).
• Immunization of women at least 2 doses

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• Arthus reactions (type III hypersensitivity
  reactions)
• For unimmunized persons gt7 yr of age, the primary
  immunization series consists of 3 doses of Td
  toxoid given intramuscularly, with the 2nd given
  4-6 wk after the 1st and the 3rd given 6-12 mo
  after the 2nd.

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Wound Management

• Tetanus prophylaxis is an essential part of all
  wound management
• All non minor wounds require human TIG except
  those in a fully immunized patient.
• TIG 250 U should be given intramuscularly, with
  500 U for highly tetanus-prone wounds (i.e.,
  unable to be debrided, with substantial bacterial
  contamination, or gt24 hr since injury).

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• IVIG
• Equine- or bovine-derived TAT 3,000-5,000 U
  surgical cleansing and debridement
• A booster is administered to injured persons who
  have completed their primary immunization series
  if (1) the wound is clean and minor but 1 0 yr
  have passed since the last booster or (2) the
  wound is more serious and 5 yr have passed since
  the last booster.

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• Persons who experienced an Arthus reaction after
  a dose of tetanus toxoid-containing vaccine
  should not receive Td more frequently than every
  10 yr, even for tetanus prophylaxis as part of
  wound management.

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• I can make a sea
• From my tears
• But alas even
• I cant believe it

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Diphteria
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Etiology

• Corynebacterium diphtheriae and rarely toxigenic
  strains of Corynebacterium ulcerans.
• Aerobic, nonencapsulated, nonspore-forming,
  mostly nonmotile, pleomorphic, gram-positive
  bacilli.
• Diphthera is Greek for leather

88

• C. diphtheriae biotypes
• Mitis, Intermedius,Belfanti,Gravis
• Ulcerans is urease-positive.
• Capable of causing diphtheria

89

• Toxigenic and nontoxigenic strains are
  indistinguishable by colony type, microscopy, or
  biochemical tests.
• Demonstration of diphtheritic toxin
• In vitro by the agar immunoprecipitin technique
  (Elek test)
• In vivo toxin neutralization test in guinea pigs
  
• PCR testing for carriage of the toxin gene

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Gram ve Bacilli and Colonies
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Diphtheria Epidemiology

• Reservoir Human carriers Usually
  asymptomatic
• Transmission Respiratory Skin and
  fomites rarely
• Temporal pattern Winter and spring
• Communicability Up to several weeks without
  antibiotics

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EPIDEMIOLOG

• C. diphtheriae is an exclusive inhabitant of
  human mucous membranes and skin.
• Spread
• Airborne respiratory droplets
• Direct contact with respiratory secretions of
  symptomatic individuals, or exudate from infected
  skin lesions.

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EPIDEMIOLOG

• Asymptomatic respiratory tract carriage is
  important in transmission.
• Where diphtheria is endemic, 3-5 of healthy
  individuals can carry toxigenic organisms.

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EPIDEMIOLOG

• Skin infection and skin carriage are silent
  reservoirs of C. diphtheriae,
• Organisms can remain viable in dust or on fomites
  for up to 6 mo.
• Transmission through contaminated milk and an
  infected food handler has been proved or
  suspected

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EPIDEMIOLOG

• Cutaneous diphtheria
• Outbreaks are associated with homelessness,
  crowding,poverty, alcoholism, poor hygiene,
  contaminated fomites, underlying dermatosis, and
  introduction of new strains from exogenous
  sources.

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PATHOGENES

• Toxigenic and nontoxigenic C. diphtheriae cause
  skin and mucosal infection, and rarely can cause
  focal infection after bacteremia.
• 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.

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PATHOGENES

• pseudomembrane
• a dense necrotic coagulum of organisms,
  epithelial cells, fibrin, leukocytes, and
  erythrocytes forms,
• Removal is difficult and reveals a bleeding
  edematous submucosa.
• Paralysis of the palate and hypopharynx is an
  early local effect of diphtheritic toxin.

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PATHOGENES

• Toxin absorption can lead to systemic
  manifestations
• kidney tubule necrosis, thrombocytopenia,
  cardiomyopathy, and/or demyelination of nerves.
• occur 2-10 wk after mucocutaneous infection, the
  pathophysiology in some cases is suspected to be
  immunologically mediated.

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CLINICAL MANIFESTATION

• RespiratoryTract Diphtheria
• Cutaneous Diphtheria
• Infection at Other Sites.

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RespiratoryTract Diphtheria

• Tonsils or pharynx (94)
• Nose and larynx the next 2 most common sites.
• average incubation period of 2-4 days
• Infection of the anterior nares, which is more
  common among infants, causes serosanguineous,
  purulent,erosive rhinitis with membrane
  formation.
• Shallow ulceration of the external nares and
  upper lip is characteristic.

101
In 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 is followed by
  unilateral or bilateral tonsillar membrane
  formation, which can extend to involve the uvula
  (which may cause toxin mediated paralysis), soft
  palate, posterior oropharynx, hypopharynx, or
  glottic areas
• Underlying soft tissue edema and enlarged lymph
  nodes can cause a bull-neck appearance.

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105

• The characteristic adherent membrane, extension
  beyond the faucial area, dysphagia, and relative
  lack of fever help differentiate diphtheria from
  exudative pharyngitis caused by Streptococcus
  pyogenes or Epstein-Barr virus.
• Vincent angina, infective phlebitis with
  thrombosis of the jugular veins, and mucositis in
  patients undergoing cancer chemotherapy are
  usually differentiated by the clinical setting.

106

• Infection of the larynx, trachea, and bronchi can
  be primary or a secondary extension from the
  pharyngeal infection.
• Hoarseness, stridor, dyspnea, and croupy cough
  are clues. Differentiation from bacterial
  epiglottitis, severe viral laryngotracheobronchiti
  s, and staphylococcal or streptococcal tracheitis
  hinges partially on the relative paucity of other
  signs and symptoms in patients with diphtheria
  and primarily on visualization of the adherent
  pseudomembrane at the time of laryngoscopy and
  intubation.

107

• Patients with laryngeal diphtheria are at
  significant risk for suffocation because of local
  soft tissue edema and airway obstruction by the
  diphtheritic membrane, a dense cast of
  respiratory epithelium, and necrotic coagulum.
• Establishment of an artificial airway and
  resection of the pseudomembrane can be
  lifesaving, but further obstructive complications
  are common, and systemic toxic complications are
  inevitable.

108
Cutaneous Diphtheria

• Classic cutaneous diphtheria is an indolent,non
  progressive infection characterized by a
  superficial, ecthymic, nonhealing ulcer with a
  gray-brown membrane.
• Diphtheritic skin infections cannot always be
  differentiated from streptococcal or
  staphylococcal impetigo, and they frequently
  coexist.

109

• In most cases, a primary process-dermatosis ,
  laceration, burns, bite, or impetigo-becomes
  secondarily infected with C. diphtheriae.
• Extremities are more often affected than the
  trunk or head. Pain, tenderness, erythema, and
  exudate are typical.
• Local hyperesthesia or hypesthesia is unusual.
  Respiratory tract colonization or symptomatic
  infection with toxic complications occurs in the
  minority of patients with cutaneous diphtheria.

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Skin Lesions
111
Infection at Other Sites.

• the ear (otitis external, the eye (purulent and
  ulcerative conjunctivitis), and the genital tract
  (purulent and ulcerative vulvovaginitis).
• Sporadic cases of pyogenic arthritis, mainly due
  to nontoxigenic strains, have been reported in
  adults and children.
• Diphtheroids isolated from sterile body sites
  should not be routinely dismissed as contaminants
  without careful consideration of the clinical
  setting.

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DIAGNOSIS

• Specimens for culture should be obtained
• The laboratory must be notified to use selective
  medium.
• Culture isolates of coryneform organisms should
  be identified to the species level, and
  toxigenicity and antimicrobial susceptibility
  tests

113
COMPLICATION

• Toxic Cardiomyopathy.
• Toxic Neuropathy

114
Toxic Cardiomyopathy.

• Toxic cardiomyopathy occurs in 10-25 of patients
  with respiratory diphtheria and is responsible
  for 50-60 of deaths.
• the risk for significant complications correlates
  directly with the extent and severity of
  exudative local oropharyngeal disease and delay
  in administration of antitoxin.

115

• The 1st evidence of cardiac toxicity
  characteristically occurs during the 2nd and 3rd
  weeks of illness as the pharyngeal disease
  improves, but can appear acutely as early as the
  1st wk, a poor prognostic sign, or insidiously as
  late as the 6th wk of illness.

116

• Tachycardia out of proportion to fever is common
  and may be evidence of cardiac toxicity or
  autonomic nervous system dysfunction.
• A prolonged PR interval and changes in the ST-T
  wave on an electrocardiographic tracing are
  relatively frequent findings dilated and
  hypertrophic cardiomyopathy detected by
  echocardiogram has been described.
• Single or progressive cardiac dysrhythmias can
  occur, including 1st, 2nd and 3rd degree heart
  block Temporary transvenous pacing may improve
  outcomes.

117

• Heart failure may appear insidiously or acutely.
• Elevation of the serum aspartat aminotransferase
  concentration closely parallels the severity of
  myonecrosis.
• Recovery from toxic myocardiopathy is usually
  complete,although survivors of more severe
  dysrhythmias can have permanent conduction
  defects.

118
Toxic Neuropathy

• Neurologic complications parallel the severity of
  primary infection and are multiphasic in onset.
• Acutely or 2-3 wk after onset of oropharyngeal
  inflammation, it is common for hypresthesia and
  local paralysis of the soft palate to occur.
• Weakness of the posterior pharyngeal, laryngeal,
  and facial nerves may follow, causing a nasal
  quality in the voice, difficulty in swallowing,
  and risk for aspiration.

119

• Cranial neuropathies characteristically occur in
  the 5th wk, leading to oculomotor and ciliary
  paralysis, which can cause strabismus, blurred
  vision, or difficulty with accommodation.
• Symmetric polyneuropathy has its onset 10 days to
  3 mo after oropharyngeal infection and causes
  principally motor deficits with diminished deep
  tendon reflexes.

120

• Distal muscle weakness in the extremities that
  progresses proximally is more commonly described
  than proximal muscleweakness with distal
  progression.
• Clinical and cerebrospinal fluid findings in the
  former are indistinguishable from those of
  Guillain-Barre syndrome. Paralysis of the
  diaphragm may ensue.
• Complete neurologic recovery is likely, but
  rarely, 2-3 wk after onset of illness, vasomotor
  center dysfunction can cause hypotension or
  cardiac failure.
• Recovery from the myocarditis and neuritis is
  often slow but usually complete. Corticosteroids
  do not diminish these complications and are not
  recommended.

121
TREATMENT

• Specific antitoxin is the mainstay of therapy and
  should be administered on the basis of clinical
  diagnosis.
• Because it neutralizes only free toxin, antitoxin
  efficacy diminishes with elapsed time after the
  onset of mucocutaneous symptoms.

122

• 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.
• Antitoxin is probably of no value for local
  manifestations of cutaneous diphtheria, but its
  use is prudent because toxic sequelae can occur.

123

• Commercially available intravenous immunoglobulin
  preparations contain low titers of antibodies to
  diphtheria toxin their use for therapy of
  diphtheria is not proven or approved.
• Antitoxin is not recommended for asymptomatic
  carriers.

124

• The role of antimicrobial therapy is to halt
  toxin production, treat localized infection, and
  prevent transmission of the organism to contacts.
• C. diphtheriae is usually susceptible to various
  agents in vitro, including penicillins,
  erythromycin, clindamycin, rifampin, and
  tetracycline. Resistance to erythromycin is
  common in populations if the drug has been used
  broadly.

125

• Only erythromycin or penicillin is recommended
  erythromycin is marginally superior to penicillin
  for eradication of nasopharyngeal carriage.
• Appropriate therapy is erythromycin (40-50
  mg/kg/day divided every 6 hr PO or IV maximum 2
  g/day), aqueous crystalline penicillin G
  (100,000-150,000 U/kg/day divided every 6 hr IV
  or 1M), or procaine penicillin (25,000-50,000
  U/kg/day divided every 12 hr 1M). Antibiotic
  therapy is not a substitute for antitoxin
  therapy. Therapy is given for 14 days.

126

• Some patients with cutaneous diphtheria have been
  treated for 7-10 days.
• Elimination of the organism should be documented
  by at least 2 successive negative cultures from
  the nose and throat (or skin) obtained 24 hr
  apart after completion of therapy.
• Treatment with erythromycin is repeated if either
  culture yields C. diphtheriae.

127
SUPPORTIVE CARE

• Cutaneous wounds are cleaned thoroughly with soap
  and water.
• Bed rest is essential during the acute phase of
  disease, usually for 2 wk until the risk for
  symptomatic cardiac damage has passed, with a
  return to physical activity guided by the degree
  of toxicity and cardiac involvement.

128
PROGNOSIS

• Protection against serious disease caused by
  imported or indigenously acquired C. diphtheriae
  depends on immunization.
• The presumed minimum is 0.01-0.10 IU/mL. In
  outbreaks, 90 of individuals with clinical
  disease have had antibody values of lt0.01 IU/mL,
  and 92 of asymptomatic carriers have had values
  of gt0.1 IU/mL.
• The risk for developing diphtheria after
  household exposure to a case is approximately 2,
  and the risk is 0.3 after similar exposure to a
  carrier.

129
Asymptomatic Case Contacts.

• All household contacts and those who have had
  intimate respiratory or habitual physical contact
  with a patient are closely monitored for illness
  through the 7 day incubation period.
• Cultures of the nose, throat, and any cutaneous
  lesions are performed.
• Antimicrobial prophylaxis is presumed effective
  and is administered regardless of immunization
  status using erythromycin (40-50 mg/kg/day
  divided qid PO for 7 days maximum 2 g/day) or a
  single injection of benzathine penicillin G
  (600,000 U 1M for lt30 kg, 1,200,000 U 1M for 30
• kg).

130

• Diphtheria toxoid vaccine, in age-appropriate
  form, is given 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.

131
Asymptomatic Carriers

• When an asymptomatic carrier is identified,
  antimicrobial prophylaxis is given for 7 days and
  an ageappropriate preparation of diphtheria
  toxoid is administered immediately if a booster
  has not been given within 1 yr.
• Individuals are placed on droplet precautions
  (respiratory tract colonization) or contact
  precautions (cutaneous colonization only) until
  at least 2 subsequent cultures obtained 24 hr
  apart after cessation of therapy are negative.

132

• Repeat cultures are performed about 2 wk after
  completion of therapy for cases and carriers,
  and, if positive, an additional 10 day course of
  oral erythromycin should be given and follow-up
  cultures performed.
• Susceptibility testing of isolates should be
  performed as erythromycin resistance is reported.
  
• Neither antimicrobial agent eradicates carriage
  in 100 of individuals.

133

• Antitoxin is not recommended for asymptomatic
  close contacts or carriers, even if inadequately
  immunized.
• Only those with an unusual contact with
  respiratory or oral secretions should be managed
  as contacts.

134
Vaccine

• Although immunization does not preclude
  subsequent respiratory or cutaneous carriage of
  toxigenic C. diphtheriae, it decreases local
  tissue spread, prevents toxic complications,
  diminishes transmission of the organism, and
  providesherd immunity when at least 70-80 of a
  population is immunized.
• DTaP, DT) contains 6.7-25.0 Lf units of
  diphtheria toxoid per 0.5 mL dose the adult
  preparation (dT) contains no more than 2 Lf units
  of toxoid per 0.5 mL dose.

135

• For children from 6 wk to 7 yr of age, five
  0.5-mL doses of diphtheria-containing (D) vaccine
  are given in a primary series, including 3 doses
  at 2, 4, and 6 mo of age, with a 4th dose,
  anintegral part of the primary series, 9-12 mo
  after the third dose.

136

• A booster dose is given at 4-6 yr of age (unless
  the 4th primary dose was administered after the
  4th birthday).
• For persons 7 yr of age and older, three 0.5 mL
  doses of diphtheria-containing (d) vaccine are
  given in a primary series of 2 doses 4-8 wk apart
  and a 3rd dose 6-12 mo after the 2nd dose.
• The only contraindication to tetanus and
  diphtheria toxoid is a history of neurologic or
  severe hypersensitivity reaction after a previous
  dose

137

• For those beginning at around1 yr of age, the
  primary series is three 0.5 mL doses of
  diphtheria containing (D) vaccine, with a booster
  given at 4-6 yr, unless the 3rd dose was given
  after the 4th birthday.
• A booster dose, consisting of an adult
  preparation of Tdap, is recommended at 11-12 yr
  of age. Adolescents 13-18 yr of age who missed
  the 11-12 year old Td or Tdap booster dose or in
  whom it has been 5 yr since the Td booster dose
  also should receive a single dose of Tdap if they
  have completed the DTPIDTaP series.

138

• There is no association of DT or dT with
  convulsions.
• Local adverse effects alone do not preclude
  continued use.
• Persons who experience Arthus-type
  hypersensitivity reactions or a temperature
  gt103F (39.4C) after a dose of dT, which is
  rare, usually have high serum tetanus antitoxin
  levels and should not be given dT more frequently
  than every 10 yr, even if a significant
  tetanusprone injury is sustained. DT or dT
  preparation can be given concurrently with other
  vaccines.

139

• Haemophi/us influenzae conjugate vaccines
  containing diphtheria toxoid (PRP-D) or the
  variant of diphtheria toxin, CRM197protein
  (HbOC), are not substitutes for diphtheria toxoid
  immunization and do not affect reactogenicity.