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Page 1Powerpoint Templates
بسم هللا الرحمن الرحیم
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Bordetella pertussis
http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm
Roxana M.Ghanaie
Ped Infectious Disease
Subspecialist
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Bordetella pertussis Basics
• Aerobic, Gram negative coccobacillus
• Alcaligenaceae Family
• Specific to Humans
• Colonizes the respiratory tract
– Whooping Cough (Pertussis)
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Bordetella pertussis
Jules Bordet
1870-1961
is a bacterium identified in 1900 byJules Bordet and Octave Gengou butisolated only in 1906 because of thedevelopment of a medium containingpotatoes extract and rabbit blood
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Why speaking about Pertussis?
• Global 2018:
• 89'000 estimated deaths (2008)
• 86% estimated DTP3 coverage
• 151'074 reported cases
• Iran pertussis incidence 2010 : 0.5/
100000
• DTP3 coverage more than 95%
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Page 6Source: WHO/IVB
pneumococcal (28%)
measles (21%)
rotavirus (16%)
Hib (15%)pertussis (11%)
tetanus (8%)
76% 24%
yellow fever (1%)
diphtheria (<1%)
polio (< 1%){
Estimated annual childhood deaths,
2002
10.5 million deaths under 5 years of age
1.4 million from diseases where vaccination is currently available
1.1 million from diseases where vaccines will be available by 2008
Meningococcal (< 1%)
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Classic Manifestation
• The incubation period of pertussis is usually
7 to 10 days, with a range of 4 to 21 days.
• “The cough of 100 days”,China,The
clinical course of illness is divided into
three stages.( age, vaccination, waning)
• The catarrhal stage is characterized by the
onset of runny nose, sneezing, low-grade
fever, and a mild cough. Cough gradually
becomes more severe (1-2 weeks)
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• The paroxysmal stage is characterized
by coughing fits (paroxysms), which may
be followed by a high-pitched inspiratory
whoop, vomiting, and/or apnea. (1-6
weeks), but may continue for 10 weeks
• The convalescent stage is characterized
by fewer paroxysmal coughing episodes
and usually disappears in 2-3 weeks, but
may continue for months.
Classic Manifestation
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Complications
• Losing weight, pneumonia, otitis, seizure,
encephalopathy, apnea
• Epistaxia, melena, subdural hematoma,
inguinal hernia, rectal prolapse,
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Infants
The severity of pertussis and the rapidity
of its progression in young infants is
effected by a number of factors such as:
the presence of transplacentally
acquired maternal antibodies to B.pertussis,
the infectious dose of bacteria that the
infant receives,
co-infection with respiratory viruses and
perhaps genetic factors related to the
pathogen or the infant.
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Infants
Short catarrhal period, longer convalescence period
Cough,feeding abn, res distress,apnea,cyanosis,
bradycardia, whoop uncommon,
paroxysms and this may lead to apnea, gasp,
hypoxia and occasionally seizures
Initially the chest is clear on auscultation but in fatal
cases B. pertussis pneumonia is always present.
Co-infection with respiratory viruses (particularly
RSV and adenoviruses) can confuse the diagnoses
because of a bronchiolitic picture (air trapping and
expiratory distress).
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Pertussis Among Adolescents and
Adults
• Accounts for up to 7-30% of cough illnesses per year
• Disease often milder than in infants and children
• Infection may be asymptomatic, or may present as classic pertussis
• Cough may last 21 d, st. paroxysmal
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Clinical manifestation in immunized
• Mild , unrecognized cough
• Prolonged cough
• Persons with mild disease may transmit the infection
• Older persons often source of infection for children
• Adults: sleep disturbances, syncope,
incontinence, rib Fx,pneumonia
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Definition:
Clinical Case Definition of Pertussis • In the absence of a more likely diagnosis a cough illness
lasting ≥2 weeks with one of the following symptoms:
• Paroxysms of coughing, OR
• Inspiratory “whoop,” OR
• Posttussive vomiting, OR
• Apnea (with or without cyanosis) (FOR INFANTS AGED
< 1 YEAR ONLY)
• OR
• clinician suspicion of pertussis
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Laboratory Criteria for Pertussis Diagnosis
• Isolation of Bordetella pertussis from a clinical specimen (culture positive), or
• Positive polymerase chain reaction (PCR)
assay for B. pertussis DNA.
Note: Serological testing for B. pertussis is not standardized ( 11 years old, 1 year after vaccination)
• Serology and DFA results should not be relied on as a criterion for laboratory confirmation of pertussis.
Definition:
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Pertussis Case Classification
• Confirmed:
– a. A positive culture for B. pertussis and an acute cough illness of any duration, or
– b. Meets the clinical case definition and is confirmed
by PCR, or
– c. Meets the clinical definition and is epidemiologically
linked directly to a case confirmed by either culture or
PCR. ( close contact in 3 weeks after cough begins)
• Probable: A case that meets the clinical case definition,
is not laboratory confirmed, and is not epidemiologically
linked to a laboratory-confirmed case; also includes
cases meeting the outbreak case definition
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Outbreaks
• Outbreak: Two or more cases involving two or more
households clustered in time (e.g., occurring within 42 days of each other) and either epi-linked or sharing a common space (e.g., in one building) where transmission is suspected to have occurred (e.g. a school).
• One case in an outbreak must be lab confirmed (PCR positive and meets case definition, or culture positive). In an outbreak setting, a case may be defined as an acute cough illness lasting ≥ 2 weeks without other symptoms.
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Transmission
• Very Contagious, 80% secondary attack rate among susceptible persons( even immunized)
• Transmission occurs via respiratory droplets, direct contact with respiratory secretions from infected individuals
• Parents are a common source of B. pertussisinfections for infants,
• grandparents, uncles ,
Aunts also provide another
potential source of infection
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Transmission
Pertussis Infectious Period:
• Most infectious during the catarrhal (early) stage.
• Infectious during the first 21 days of cough if not
treated with appropriate antibiotic.
• No longer infectious after 5 days of treatment with
appropriate antibiotic
• Length of communicability: age, immunization status,
appropirate antibiotic therapy
• Isolation: standard, droplet
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B. parapertussis
• B. parapertussis infection in humans can cause unrecognized infection, mild
pertussis, or classic pertussis
• B. bronchisepica
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DD prolonged cough
• Adenovirus
• Para influenza
• Influenza A,B
• M.pneumonia
• RSV
• C.trachomatis
• C. pneumonia
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• Laboratory confirmation of pertussis is
difficult and delayed. Therefore, clinicians
need to make the diagnosis of
• pertussis presumptively in patients with a
history of intense paroxysmal or chronic
coughing with or without whooping, color
changes, posttussive vomiting, incomplete
or absent pertussis vaccination, and
finding of lymphocytosis on laboratory
examination.
DD
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DD prolonged cough
• spasmodic attacks of coughing may be
observed in children with:
• bronchiolitis, bacterial pneumonia, cystic
fibrosis, or tuberculosis. Afebrile
Pneumonia Syndrome
• The cough associated with: sinusitis,
airway foreign body
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CXR Indications
• 1/ <1y
• 2/ toxic
• 3/ progressive cough>3 w
• 4/ res distress
• 5/ probable underlying dis( CF, CHD,forign
body, Hilar LAD)
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Chest Xray
• Most common : Normal
• Shaggy heart( central airway not periph)
• Hyperinflation, hyper lucent lung
• Micro athelectasia
• Secondary bac. Pneumonia
• Bronchiolitis oblitrans( adeno, influ,
measles, pertussis)
• pneumothorax
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Management:
• The desired outcomes are:observing the severity of cough
limiting the number of paroxysms,
providing assistance when necessary,
maximizing nutrition, rest, and recovery,
follow the course of disease
prevent/treat complications
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• Admitt:
1- all infants<3 m despite severity & all 3-6 m except
the attacks are mild as observed by physician
2- with complications(intractable nausea and
vomiting, failure to thrive,seizures, encephalopathy,
or for patients with sustained hypoxemia during
coughing paroxysms who require supplemental
oxygen,) hx of prematurity in infant, with underlying
cardiac, pul, neuromuscular dis
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Management
• For the hospitalized patient, in addition to
standard precautions, droplet precautions
are recommended
• Monitor heart rate, respiratory rate, and
oxygen saturation of hospitalized patients
continuously,especially in relation to
coughing paroxysms. Coughing, feeding,
vomiting, and weight changes should be
recorded.
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Management:
• Oxygen,suction,hydration, nutrition
• Patients who are severely ill may require treatment in
an ICU.
• Investigate all probable, pertussis reports. Evaluate
whether reported case’s symptoms are compatible
with pertussis
• Recommend antibiotics for the index case (first case
reported to public health authorities), all household
and close contacts. Antibiotic inspite of age,
immunization Hx
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Report & find contacts
• Only confirmed and probable cases are
reported.
• Recommend DTaP/Tdap vaccination
according to appropriate age for exposed
children, adolescents and adults.
• Exposed children < 7 years of age whose last
DTP( 4th dose) was more than 3 years ago
should be vaccinated.( more than 6m after 3rd
dose)
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• Evaluate close contacts for pertussis
symptoms, and when possible collect
specimens for lab testing from
symptomatic persons
• Vaccine after discharge:
If documented disease, do not need additional doses of pertussis vaccine
Satisfactory documentation of disease:
recovery of B. pertussis on culture, OR typical symptoms and clinical course when epidemiologically linked to a culture- proven case
Report & find contacts
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Treatment (cont)
During catarrhal stage ameliorate disease
After cough establishment, does not
generally lessen duration; protect others
Limited benefit if begun >21 days after
onset/exposure
Exception: high risk cases/contacts -
treat up to 6 weeks
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Treatment
• Antibiotic therapy
– Erythromycin
– Azithromycin
– Clarithromycin
http://www.aboutthatbug.com/AboutThatBug/files/CCLIBRARYFILES/
FILENAME/0000000032/033_lg.jpg http://www.vet.purdue.edu/bms/courses/lcme510/chmrx/macrohd.htm
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Treatment
Erythromycin
For children: 40-50 mg/kg/d in 4 divided doses;10-14 days
• For adults: 1 to 2 g/day given every 6 h
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Treatment
Azithromycin
• for children: at 10 mg/kg on day 1 and 5
mg/kg on days 2 to 5 as a single dose
for 5 days
• 10-12 mg/kg/d PO in 1 dose for a total of 5
days. ( < 6m)
• for adults: 500 mg on day 1 and 250 mg
on days2 to 5
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Treatment
Clarithromycin
• for children: at 15 to 20 mg/kg/day in two
divided doses for 7 days
• for adults: 1 g/day in two doses for 7 days
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Treatments
Trimethoprim(T)/Sulfamethoxazole (S)
8mg/kg T + 40 mg/kg S/d in 2
divided doses; 14 days
• Erythromycin and clarithromycin are not
recommended in infants younger than 4-6 w
because their use has been associated with
increased risk for infantile hypertrophic pyloric
stenosis (IHPS).
• Resistant to macrolid: rare
• Cephalosporine, PN not effective
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Treatment
• Humans infected with B. parapertussis or B. holmesii
• macrolide therapy indicated above.
• In contrast, however, B. bronchiseptica is usually resistant to Erythromycin Most
sensitive to aminoglycosides, extended-
spectrum third-generation penicillins,
tetracyclines, quinolones, and trimethoprim-
sulfamethoxazole.
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Treatment
• It has been observed in numerous small
studies that pertussis infant deaths relate
directly to the degree of leukocytosis
• double volume exchange transfusion, to
lower the white blood cell count
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Treatment
• Pertussis-specific immune globulin is an
investigational product that may be
effective in decreasing paroxysms of
cough but requires further evaluation.
• The use of corticosteroids, albuterol, and
other beta2-adrenergic agents for the
treatment of pertussis is not
supported by controlled, prospective data
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Exclusions from
work/school
Symptomatic: first 5 days of treatment
Symptomatic, refuses treatment:
exclude for 21 days from onset of
symptoms
Asymptomatic exposure: no exclusion
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Complications in Infants
• Pneumonia( in 22% infants)
• Seizures( in 2% infants)
• Encephalopathy( less than 0.5%
infants)
• FTT,Death 0.3%( 1% in less than 2 m-
old)
• SIDS( ???)
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Prognosis
• Prognosis for full recovery is excellent; however, patients
with comorbid conditions as previously described have a
higher risk of morbidity and mortality
• Leukocytosis, particularly WBC counts of more than
100,000, has been associated with fatalities from
pertussis.
• Another study showed that WBC counts of more than
55, 000 and pertussis complicated by pneumonia were
independent predictors of fatal outcome in a multivariate
model.
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Use a narrow definition of
close contact
Close contacts:
• Household contacts;
• Other persons having direct prolonged exposure
to the case while case was contagious and was
coughing or sneezing.
1. Direct face-to-face contact for an undefined time
period with an infectious pertussis case (case
coughing < 21 days and has not completed 5 days of
appropriate antibiotic treatment).
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Use a narrow definition of
close contact
2. . Shared confined space in close proximity for a
prolonged period of time, such as ≥ 1 hour, with an
infectious pertussis case. For example, riding in a car
with a pertussis case.
3. Direct contact with respiratory, oral, or nasal
secretions from an infectious pertussis case (e.g., an
explosive cough or sneeze in the face, sharing food, sharing eating
utensils, kissing, mouth-to-mouth resuscitation, or performing a full
medical exam including examination of the nose and throat without
wearing a mask). Summary of Pertussis Investigation and Control Guidelines Colorado Department of Public Health and Environment
Communicable Disease Epidemiology Program
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Exposed
• Household, close contacts, health care worker:
• Check immunization, initiate, complete
• Chemopx for all contacts regardless age,
immunization
• If start later than 21 d after exposure, give only to
highrisk: young infant, pregnant, care taker of infants
• Monitor for 21 d after last contact, for symptoms
• Evalute symptomatic exposed persons and exclude
from public setting and report confirmed, probable
cases
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Management
1/ Critical care needs
2/ Neutrilize toxin
3/ Eradicate C. diphtheria
4/ Complications
• Mechanical ventilation (combination of
airway obstruction by the diphtheritic
membrane and peripharyngeal edema )
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Anti toxin
• Specific antitoxin is the mainstay of
therapy and should be administered on the
basis of clinical diagnosis
• neutralizes free toxin only.
• Efficacy diminishes with elapsing time
after the onset of mucocutaneous
symptoms.
• Only an equine preparation is available
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Anti toxin
• Antitoxin is administered once at an
empiric dose based on the degree of
toxicity, site and size of the membrane,
and duration of illness.
• Most authorities prefer the intravenous
route, with infusion over 30-60 minutes.
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Anti toxin
• Antitoxin is probably of no value for local
manifestations of cutaneous diphtheria,
but its use is prudent because toxic
sequelae can occur.
• Commercially available IVIG ,contain
antibodies to diphtheria toxin; is not
proved or approved
• Antitoxin is not recommended for
asymptomatic carriers.
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Antitoxin
دت محل و اندازه غشای دیفتری، شدوز تزریقی ضد سم بر اساس •
:تعیین می شوداثرات سم و مدت زمان شروع بیماری
ط تا وجود لنفادنوپاتی گردنی منتشر و نرم نشاندهنده جذب متوس•
شدید سم است
48درگیری حلق و یا حنجره بمدت کمتر و یا مساوی •
واحد40000-20000ساعت،
واحد60000-40000درگیری نازو فارنژیال •
روز و یا بیشتر و یا تورم 3بیماری شدید یا گسترده یا بمدت •
واحد120000-80000شدید گردن
40000-20000در دیفتری پوستی معموال اثر ندارد ولی بعضی •
واحد را توصیه می کنند
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Antimicrobial
• Eradication, prevent transmission, halt toxin production
• C diphtheriae is usually susceptible to various agents in vitro, including penicillin,erythromycin, clindamycin,
rifampin, and tetracycline.
• Penicillin and erythromycin are only recommended for
treatment.
• Erythromycin is marginally superior to penicillin for
eradication of nasopharyngeal infection.
• Resistance to erythromycin is common in closed
populations if the drug has been used broadly
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Antimicrobial
-40) روز14بمدت اریترو مایسین خوراکی و یا تزریقی •
(گرم در روز2بازای هر کیلوگرم وزن، حداثر 50
واحد بازای هر 100-150000-تزریقی Gپنی سیلین •
داخل وریدی برای مدت ( دوز4کیلوگرم وزن منقطع در
روز14
25-50000) تزریقی عضالنی پروکایین Gپنی سیلین •
واحد بازای هر کیلوگرم وزن بدن روزانه در دو دوز
روز14بمدت ( منقسم
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Antimicrobial
• Antibiotic therapy is not a substitute for
antitoxin therapy.
• Elimination of the organism should be
documented by at least 2 successive
cultures from the nose and throat (or skin)
obtained 24 h apart after completion of
therapy.
• Treatment with erythromycin is repeated if
culture results remain positive
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Vaccine
• Diseases dose not produce immunity,
vaccinate the patient in convalescent
period
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Surgical Care
• Otolaryngeal assessment is needed in
patients with severe respiratory or
neurologic complications or as part of
critical care.
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Consultation
Cardiologist:
Elevation of serum AOTclosely parallels the
severity of myonecrosis.
arise during the first 10 days of illness or may be
delayed until 2-3 weeks after
In electrocardiographic tracings, a prolonged PR
interval, changes in the ST-T wave, and single
or progressive cardiac dysrhythmias can occur,
such as first-degree, second-degree, and third-
degree heart block, atrioventricular dissociation,
and ventricular tachycardia.
Toxic cardiomyopathy and myocarditis
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• Neurologist:
• parallel the extent of primary infection and
are multiphasic in onset.
• Hypesthesia and local paralysis of the soft
palate
• Weakness of the posterior pharyngeal,
laryngeal, and facial nerves , causing a
nasal tone in the voice, difficulty
inswallowing, and risk of death from
aspiration.
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Neuropathy
• Cranial neuropathies characteristically occur in
the fifth week and lead to oculomotor and ciliary
paralysis, which manifest as strabismus, blurred
vision, or difficulty with accommodation.
• Symmetric polyneuropathy begins within 10
days to 3 months after oropharyngeal infection,
motor function deficit with diminished deep
tendon reflexes. DD polyneuropathy of Landry-
Guillain-Barré syndrome.
• Paralysis of the diaphragm can ensue.
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Close contact
• Promptly identify close contacts of patients
in whom diphtheria is suspected. in the
household and other persons with a
history of habitual close contact with the
patient.
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Close contact
• For close contacts, irrespective of their
immunization status, the following measures
should be taken:
• Surveillance for 7 days for evidence of disease
• Culture for C diphtheriae
• Antimicrobial prophylaxis with oral erythromycin
(40-50 mg/kg/d for 7 d; not to exceed 2 g/d) or a
single intramuscular injection of penicillin G
benzathine (600,000 U for children who weigh <
30 kg and 1.2 million U for children weighing >30
kg and adults)
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Carrier
• Obtain repeated pharyngeal cultures from contacts
proven to be carriers at a minimum of 2 weeks after
completion of therapy.
• Asymptomatic, previously immunized, close contacts
should receive a booster dose of a preparation
containing diphtheria toxoid (DTaP, DT, Tdap, or Td,
depending on age) if they have not received a booster
• dose of diphtheria toxoid within 5 years. Immunize
children in need of the fourth dose.
Contacts who cannot be kept under surveillance should
receive benzathine penicillin G (not erythromycin),
• and a dose of , DT, or Td (administered if the patient has
not received a booster injection within 1 year)
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Mortality/Morbidity
• Death due to mechanical airway
obstruction or cardiac involvement with
circulatory collapse
• In at least 10% of patients with respiratory
tract diphtheria
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Mortality/Morbidity
Prognosis depends on:
• The virulence of the organism (with the gravis
strain usually accounting for the most
severedisease),
• The age and immunization status of the
patient,
• The site of involvement,
• The speed with which antitoxin is administered
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Mortality/Morbidity
• Airway obstruction by the diphtheritic
membrane and peripharyngeal edema
combine to pose a risk of death in patients
with diphtheria.
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Mortality/Morbidity
• For patients in whom disease is
recognized on day 1 and therapy is
promptly initiated, the mortality rate is
approximately 1%.
• If appropriate treatment is withheld until
day 4, the mortality rate rises to 20%
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Mortality/Morbidity
• Toxic cardiopathy occurs in approximately
10-25% of patients with diphtheria and is
responsible for 50-60% of deaths.
• Neurologic complications parallel the
extent of primary infection and are
multiphasic in onset.