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