D p t

1. DR. V . VEERA RATNAKAR REDDY
Senior resident

2. Corynebacterium diphtheriae
Aerobic gram-positive
bacillus
Typical shape n granules
distinguishing features
from normal
diphtheroid.
toxin production &
relation with phase
infection.

3. Diphtheria Epidemiology
Reservoir Human carriers
Usually asymptomatic
Transmission aerosols, droplets ,
Skin lesions
Temporal pattern Winter and spring
Communicability Up to several weeks
without antibiotics

4. Diphtheria Clinical Features
Incubation period 2-5
days
(range, 1-10 days)
based on site of
infection
anterior nasal
Ocular
Pharyngo-tonsillar
laryngeal
cutaneous
genital

5. 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 -???

6. Tonsillar Diphtheria

7. Diphtheria Complications
Mostattributabletotoxin
Severitygenerallyrelatedtoextentoflocaldisease
Mostcommoncomplications:
myocarditis–2
nd
week
neuritis-3
rd
week
Deathoccursin5%-10%forrespiratorydisease

9. Diphtheria vaccine
Detoxifiedbacterial,proteintoxin
Injectable,IMadministration
ToxigenicCorynebacteriumdiphtheriae(infected
withbphage)
Neutralizesonlyunboundtoxin
LifetimeofAb:15days–3weeks,wait3-4weeks
beforegivingtoxoid.Onlygivenonce.

10. Manufacturing Process
ToxigenicstrainofC.diphtheriaegrownin
Fentonmediumwithabovineextract
Toxoidedbyincubationwithformaldehydefor
severalweeks
Purifiedbyprecipitation,dialysisandsterile
filtered
Adsorbedontoaluminumhydroxide,Al(OH)
3

11. Diagnosis & treatment
Alberts 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

12. ROLE OF ANTIBIOTICS:
ADS
14DAYCOURSE:BENZYL/PP4
REPEATSWAB&RX
MANAGEMENT OFCARRIER:
benzathinepenicillin
Managementofcontacts:
erythromycin/BP

13. Diphtheria Toxoids Adverse Reactions
Localreactions(erythema,induration)
Exaggeratedlocalreactions(Arthus-type)
Feverandsystemicsymptomsnotcommon
Severesystemicreactionsrare

14. Pertussis (Whooping Cough)
Highlycontagiousrespiratoryinfectioncausedby
Bordetellapertussis.
Fastidious gram-negative bacteria.
Antigenic and biologically active components:
pertussistoxin(PT)
filamentoushemagglutinin(FHA)
agglutinogens
adenylatecyclase
pertactin
trachealcytotoxin

15. Pertussis Epidemiology
Reservoir Adolescents and adults
Transmission Respiratory droplets
CommunicabilityMaximum in catarrhal stage
Secondary attack rate-upto 80%

16. Pertussis Pathogenesis
•B.pertussisbindstoandmultipliesonciliatedcells
(respiratorymucosa).Theinfectionisnotsystemic.
•B.pertussisbindsviaatleast2adhesionproteinstothe
ciliatedcells
•Filamentoushemagglutinin
•Pertussistoxin(Ptx,A5Bexotoxin)

17. 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

18. 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

19. PertussisComplications*
Condition
Pneumonia
Seizures
Encephalopathy
Hospitalization
Death
Percent reported
4.9
0.7
0.1
16
0.2
*Cases reported to CDC 2001-2003 (N=28,998)

20. Pertussis Complications by Age0
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
Percent
Pneumonia Hospitalization
*Cases reported to CDC 1997-2000 (N=28,187)

21. Pertussis (vaccines)
Killed Whole cell -
still used in developing countries
relatively cheap
Acellular (aP) -
currently licensed in U.S., Japan and Europe
some are recombinant
expensive

22. Pertussis-containing Vaccines
DPT(pediatric)
approvedforchildren6weeksthrough6years(toage7years)
containssameamountofdiphtheriaandtetanustoxoidaspediatricDT
Tdap(adolescentandadult)
approvedforpersons10-18years(Boostrix)and11-64years(Adacel)
containslesseramountofdiphtheriatoxoidandacellularpertussis
antigenthanDTaP

23. Tetanus
First described by
Hippocrates
Etiology discovered in
1884 by Carle and
Rattone
Anaerobic, GP, spore
forming, char . Shape

24. Tetanus Epidemiology
Reservoir Soil and intestine of
animals and humans
Transmission Contaminated wounds
Tissue injury
Temporal pattern Peak in summer or
wet season
Communicability Not contagious

25. pathogenesis:
Toxintravelsupnerveendingsbyintra-axonal
transport
Gainsentrytoneuromuscularjunctionsbybindingto
gangliosidesinhibitingGABArel.&synaptobrevin.
Interfereswithreleaseofneurotransmittersfrom
presynapticinhibitoryfibers
Excitatoryreflexesmultiplyunchecked,causing
spasms

26. Tetanus toxins
Tetanolysin-possibleroleinestablishinginfectionat
inoculationsite
Tetanospasmin:
accumulatesintracellularlyduringlog-phasegrowth
releasedintomediumuponautolysis
Minimumhumanlethaldose~2.5ng/kg

28. 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.

29. Tetanus disease
Tetanospasms
localized -spasm of muscles close to site of
injection; weeks to months duration; rare but may
precede generalized symptoms
generalized -80% of cases
Complications of the spasms:
fractures of the long bones and vertebrae
asphyxia from glottic obstruction

31. Neonatal Tetanus
Generalized tetanus in newborn infant
Infant born without protective passive immunity
Estimated >215,000 deaths worldwide in 1998
Complications
Laryngospasm
Fractures
Hypertension
Nosocomialinfections
Pulmonary embolism
Aspiration pneumonia
Death

32. Tetanus Toxoid
Formalin-inactivated tetanus toxin
ScheduleThree or four doses + booster
Booster every 10 years
EfficacyApproximately 100%
DurationApproximately 10 years
Should be administered with diphtheria toxoid as
DTaP, DT, Td, or Tdap

33. Dose
Primary 1
Primary 2
Primary 3
BOOSTER
Age
6 WEEKS
10 WEEKS
14 WEEKS
15-18 months
Routine DPT Primary Vaccination Schedule
4-6 yrs ( dTP)
11-12 yrs (tt/ td)
Every 10 yrs( tt)

37. Interchangeability of Different Brands of DTP Vaccine
Wheneverfeasible,thesameDTaPvaccine
shouldbeusedforalldosesoftheseries
Limiteddatasuggestthat“mixandmatch”
DTaPschedulesdonotadverselyaffect
safetyandimmunogenicity
Ifvaccineusedforearlierdosesisnot
knownornotavailable,anybrandmaybe
usedtocompletetheseries

38. DPT Adverse Reactions
Localreactions :20%-40%
(pain,redness,swelling)
Tempof101
o
F :3%-5%
orhigher
Moresevereadversereactions:notcommon
Localreactionsmorecommonfollowing4
th
and
5
th
doses.

39. DPT Contraindications
Severeallergicreactiontovaccinecomponentor
followingapriordose
Encephalopathynotduetoanotheridentifiable
causeoccurringwithin7daysaftervaccination

40. Rationale for a Tdap Vaccination Program for
Adolescents and Adults
Primary
To protect the vaccinated adolescent and adult from
pertussis
Secondary
To reduce the reservoir B. pertussisand thereby
reduce
Spread of B. pertussisto 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

41. DPT Precautions*
Moderate or severe acute illness
Temperature >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

42. 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)

43. ACIP Recommendations for Tdap Adolescents
Adolescents11-12yearsofageshouldreceivesingle
doseofTdap(insteadofTd),iftheyhavecompleted
therecommendedchildhoodDTaPvaccinationseries
Those13-18yearsofagewhohavenotyetreceivedyet
receivedaTdshouldreceiveasingledosealso.

44. Adolescents11-18yearswhohavealreadyreceivedTd
areencouragedtoreceiveasingledoseofTdap,to
provideprotectionagainstpertussis,iftheyhave
completedtherecommendedchildhoodDTaP
vaccinationseries
A5yearintervalisencouragedtoreducethechance
ofalocalreaction