DR. V . VEERA RATNAKAR REDDY Senior resident
Corynebacterium diphtheriaeAerobic gram-
positive bacillus Typical shape n
granules distinguishing
features from normal diphtheroid.
toxin production & relation with phase infection.
Diphtheria Epidemiology
Reservoir Human carriers Usually asymptomatic
Transmission aerosols, droplets , Skin lesions
Temporal pattern Winter and spring
Communicability Up to several weekswithout antibiotics
Diphtheria Clinical FeaturesIncubation period
2-5 days (range, 1-10 days)
based on site of infectionanterior nasalOcular Pharyngo-tonsillar laryngealcutaneousgenital
Pharyngeal and Tonsillar Diphtheria
Insidious onset
Exudate spreads within 2-3 days and may
form adherent membrane
Pseudomembrane: fibrin, bacteria, and
inflammatory cells, no lipid
Fever usually not high but patient appears
toxic
Differntial diagnosis - ???
Tonsillar Diphtheria
Diphtheria Complications
Most attributable to toxin
Severity generally related to extent of local
disease
Most common complications :
myocarditis – 2nd week
neuritis - 3rd week
Death occurs in 5%-10% for respiratory disease
Diphtheria vaccineDetoxified bacterial, protein toxin
Injectable, IM administration
Toxigenic Corynebacterium diphtheriae
(infected with phage)
Neutralizes only unbound toxin
Lifetime of Ab: 15 days – 3 weeks, wait 3-4
weeks before giving toxoid. Only given once.
Manufacturing ProcessToxigenic strain of C. diphtheriae grown in
Fenton medium with a bovine extract
Toxoided by incubation with formaldehyde
for several weeks
Purified by precipitation, dialysis and sterile
filtered
Adsorbed onto aluminum hydroxide,
Al(OH)3
Diagnosis & treatmentAlberts staining
Smear & culture
Modified ELEK
test
Rapid EIA.
ANTI TOXIN DOSES( IU)
Pharyn/laryn: 20k-40k
Cutaneous: 20k-40k
Nasopharyn: 40k-60k
Severe cases: 80k- 1.2
lakh
ROLE OF ANTIBIOTICS:ADS
14 DAY COURSE: BENZYL/ PP4
REPEAT SWAB & RX
MANAGEMENT OF CARRIER :
benzathine penicillin
Management of contacts:
erythromycin/ BP
Diphtheria Toxoids Adverse Reactions
Local reactions (erythema, induration)
Exaggerated local reactions (Arthus-type)
Fever and systemic symptoms not
common
Severe systemic reactions rare
Pertussis (Whooping Cough)Highly contagious respiratory infection
caused by Bordetella pertussis.Fastidious gram-negative bacteria.Antigenic and biologically active
components:
pertussis toxin (PT)
filamentous hemagglutinin (FHA)
agglutinogens
adenylate cyclase
pertactin
tracheal cytotoxin
Pertussis Epidemiology
Reservoir Adolescents and adults
Transmission Respiratory droplets
Communicability Maximum in catarrhal stage
Secondary attack rate- upto 80%
Pertussis Pathogenesis
• B. pertussis binds to and multiplies on ciliated cells
(respiratory mucosa). The infection is not systemic.
• B. pertussis binds via at least 2 adhesion proteins to the
ciliated cells
•Filamentous hemagglutinin
•Pertussis toxin (Ptx, A5B exotoxin)
Pertussis Clinical Features
Incubation period 5-10 days (range 4-21 days)
Insidious onset, similar to minor
upper respiratory infection with nonspecific cough
Fever usually minimal throughout course of illness
Catarrhal stage : 1-2 weeks
Paroxysmal cough stage: 1-6 weeks( contagious)
Convalescence: Weeks to months
Pertussis Among Adolescents and Adults
Disease often milder than in infants and children
Infection may be asymptomatic, or may present
as classic pertussis.
Persons with mild disease may transmit the
infection
Older persons often source of infection for
children
ConditionPneumoniaSeizuresEncephalopathyHospitalizationDeath
Percent reported4.90.70.1160.2
*Cases reported to CDC 2001-2003 (N=28,998)
Pertussis Complications by Age
0
10
20
30
40
50
60
70
<6 m 6-11 m 1-4 y 5-9 y 10-19 y 20+ y
Age group
Perc
en
t
Pneumonia Hospitalization
*Cases reported to CDC 1997-2000 (N=28,187)
Pertussis (vaccines)
Killed Whole cell -still used in developing countriesrelatively cheap
Acellular (aP) - currently licensed in U.S., Japan and Europesome are recombinantexpensive
Pertussis-containing VaccinesDPT (pediatric)
approved for children 6 weeks through 6 years (to age 7 years)
contains same amount of diphtheria and tetanus toxoid as
pediatric DT
Tdap (adolescent and adult)
approved for persons 10-18 years (Boostrix) and 11-64 years
(Adacel)
contains lesser amount of diphtheria toxoid and acellular
pertussis antigen than DTaP
Tetanus
First described by
Hippocrates
Etiology discovered
in 1884 by Carle and
Rattone
Anaerobic, GP, spore
forming, char . Shape
Tetanus EpidemiologyReservoir Soil and intestine of
animals and humans
Transmission Contaminated wounds Tissue injury
Temporal pattern Peak in summer orwet season
Communicability Not contagious
pathogenesis:
Toxin travels up nerve endings by intra-axonal
transport
Gains entry to neuromuscular junctions by
binding to gangliosides inhibiting GABA rel .&
synaptobrevin.
Interferes with release of neurotransmitters from
presynaptic inhibitory fibers
Excitatory reflexes multiply unchecked, causing
spasms
Tetanus toxins
Tetanolysin - possible role in establishing
infection at inoculation site
Tetanospasmin:
accumulates intracellularly during log-phase
growth
released into medium upon autolysis
Minimum human lethal dose ~ 2.5 ng/kg
Tetanus Clinical Features Incubation period; 8 days
(range, 3-21 days)
Generalized tetanus: descending symptoms of
trismus (lockjaw), difficulty swallowing, muscle
rigidity, spasms
Spasms continue for 3-4 weeks; complete
recovery may take months
Fatality rate ~90% w/o Rx & 30% with Rx.
~30% w/ treatment
Tetanus disease
Tetanospasmslocalized - spasm of muscles close to site of
injection; weeks to months duration; rare but may precede generalized symptoms
generalized - 80% of casesComplications of the spasms:
fractures of the long bones and vertebraeasphyxia from glottic obstruction
Neonatal TetanusGeneralized tetanus in newborn infant Infant born without protective passive immunityEstimated >215,000 deaths worldwide in 1998
ComplicationsLaryngospasmFracturesHypertensionNosocomial infectionsPulmonary embolismAspiration pneumoniaDeath
Tetanus ToxoidFormalin-inactivated tetanus toxin
Schedule Three or four doses + boosterBooster every 10 years
Efficacy Approximately 100%
Duration Approximately 10 years
Should be administered with diphtheria toxoid as DTaP, DT, Td, or Tdap
DosePrimary 1Primary 2Primary 3BOOSTER
Age6 WEEKS
10 WEEKS14 WEEKS
15-18 months4-6 yrs ( dTP)
11-12 yrs (tt/ td) Every 10 yrs( tt)
Interchangeability of Different Brands of DTP Vaccine
Whenever feasible, the same DTaP vaccine should be used for all doses of the series
Limited data suggest that “mix and match” DTaP schedules do not adversely affect safety and immunogenicity
If vaccine used for earlier doses is not known or not available, any brand may be used to complete the series
DPT Adverse Reactions
Local reactions : 20%-40%
(pain, redness, swelling)
Temp of 101oF : 3%-5%
or higher
More severe adverse reactions : not common
Local reactions more common following 4th
and 5th doses.
DPT Contraindications
Severe allergic reaction to vaccine
component or following a prior dose
Encephalopathy not due to another
identifiable cause occurring within 7 days
after vaccination
Rationale for a Tdap Vaccination Program for Adolescents and Adults
PrimaryTo protect the vaccinated adolescent and adult
from pertussis
SecondaryTo reduce the reservoir B. pertussis and
thereby reduceSpread of B. pertussis to persons at risk of
severe pertussis (e.g., infants aged <12 months, adults with co-morbid conditions)
Cost and disruption of pertussis in health care facilities and other institutional settings
DPT Precautions*Moderate or severe acute illnessTemperature >105°F (40.5°C) or higher
within 48 hours with no other identifiable cause
Collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours
Persistent, inconsolable crying lasting >3 hours, occurring within 48 hours
Convulsions with or without fever occurring within 3 days
*may consider use in outbreaks
DTaP Vaccine FormulationsComponent,
per 0.5 ml dose GSK
Infanrix, Pediarix
AP Inc (sanofi pasteur)
Tripedia
AP LTd (sanofi pasteur) Daptacel
Diphtheria Toxoid 25 Lf 6.7 Lf 15 Lf
Tetanus Toxoid 10 Lf 5 Lf 5 Lf
PT, inactivated 25 g 23.4 g 10 g
FHA, inactivated 25 g 23.4 g 5 g
PRN (69kD OMP) 8 g 3 g Fimbriae 2 Fimbriae 3
0 0 5 g
2-phenoxyethanol (PE), preservative
2.5 mg 0 0.6%
NaCl 4.5 mg
Aluminum adjuvant <0.625 mg <0.17 mg 0.33 mg
Formaldehyde, residual
100 g <100 g < 0.02%
Glutaraldehyde, residual
< 0.1%
Polysorbate 80 (Tween 80)
100 g
Thimerosal, preservative
0 Trace (single-dose) 25 g/dose (multi-vial)
ACIP Recommendations for Tdap Adolescents
Adolescents 11-12 years of age should
receive single dose of Tdap (instead of Td), if
they have completed the recommended
childhood DTaP vaccination series
Those 13-18 years of age who have not yet
received yet received a Td should receive a single
dose also.
Adolescents 11-18 years who have already
received Td are encouraged to receive a single
dose of Tdap, to provide protection against
pertussis, if they have completed the
recommended childhood DTaP vaccination series
A 5 year interval is A 5 year interval is encouragedencouraged to reduce the to reduce the
chance of a local reactionchance of a local reaction
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