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Whooping Cough

Bordetella
Pertussis Infection

Dr.T.V.Rao MD
A Tribute to Bordet - Gengou
What is Whooping cough
 Whooping Cough (Pertussis) is a
bacterial infection of the lungs which
is caused by a bacterium Bordetella
pertussis. It is a very contagious
disease which causes coughing with
little or no fever. The coughing may
be so severe that it leads to vomiting
and aspiration.
How the name Whooping derived
 Whooping cough is an infectious
bacterial disease that causes
uncontrollable coughing. The name
comes from the noise you make
when you take a breath after you
cough. You may have choking spells
or may cough so hard that you
vomit.
Identification of Bordetella
 Jules Bordet and Gengou contributed for
discovery 1900
 Identified as samll bacilli in children with
Whooping cough.
 Bordetella pertussis ( Intense cough )
 Other related Bacteria
B.parapertussis
B.brochoseptica
B.avium
Bordetella pertussis ( B G bacillus )
 Gram negative
organism
 Small,
ovoid,cocobacillus.
 Lengh is 0.5
microns
 Have bipolar
metachromatic
granules when
stained with
Toludine blue
Bordetella pertussis ( B G bacillus)
 Small ovoid
coccobacillus 0.5
microns
 On repeated cultures
becomes become
larger thread like
bacilli.
 Non motile, Non
sporing
 Capsulated – loose on
repeated culturing
Other characters
 Donot swell in the
presence of antigen.
 Loose clumps of bacilli
appear as thumb print
appereance with clear
space between the
organisms.
 Freshly isolated
strains have fimbria.
Culture Characters
 Aerobic Not anaerobic
 Grows optimally at 350
to
370 c
 Preferred medium –
Bordet Gengou
glycerin potato blood
agar
 Blood for neutralizing
inhibitory substances
formed during
bacterial grwoth.
 Charcoal also serves
the same purpose.
Mercury Drop colonies on
Bordet-Gengou Medium
 Grwoth takes
longer upto 48 –
72 hours
 On blood agar
appear as small
dome shaped
opaque viscid
grayish white
retractile
glishninttg
 Resembles bisected
pearly or mercury
drops
Aluminum paint appearance
 Colonies
surrounded by
hazy zone of
hemolysis
 Confluent grwoth
presents as
aluminum paint.
Biochemical Reactions
 In active – donot
ferment sugars
 Indole test +
 Reduce Nitrates
 Utilize citrates
 Splits urea
 Catalase +
 Oxidase +
Resistance
 Killed by heat at 550c for 30 mt
 Drying and disinfectants kill the
organism
 Survive outside for 5 days
 3 days on cloths
 Few hours on paper
Antigenic characters and
Virulence
 Agglutinogens - Species specific
surface agglutinogens with capsule K
antigens or fimbria
 14 agglutinin factors are identified
 Factors 7 is common in all species
 Factor 1- 6 in only B pertussis
 Factor 12 in B.brochoseptica
 Factor 14 in B parapertussis
Virulence factors
 These virulence factors include
adhesions such as filamentous hem
agglutinin, agglutinogens, peractin,
and fimbriae as well as a number of
toxins including pertussis toxin,
adenylate cyclase toxin, trachael
cytotoxin, Dermonecrtoic toxin and
heat-labile toxin (CDC, 2005).
Pathogenesis of B.pertussis
 Like most Gram
negative
pathogens, B.
pertussis also
contains a
Lipopolysaccharide
coat that acts as
an Endotoxin and
can aid colonization
by agglutinating
human cells
(Steele, 2004).
Virulent Molecules
Toxin – cellular action.
Mechanism of Infection
 1,2,3 are common
infective strains
vaccines contain all
the three
Agglutinogens
promoting
virulence by
helping bacteria to
attach to
respiratory
epithelial cells
Pertussis Toxin
 Pertussis toxin – MW 1,17,000
 Hexamer protein composed of 6
subunits with A – B structure
 A has enzymatic activity it can be
toxoided
 Pertussis toxin is the major
component of Acellular Pertussis
vaccine.
Nature of Toxin
 It produces a highly lethal toxin
(formerly called Dermonecrtoic toxin)
which causes inflammation and local
necrosis adjacent to sites where B.
pertussis is located. The lethal toxin
is a 102 kDa protein composed of
four subunits, two with a mw of
24kDa and two with mw of 30 kDa.
Pertussis Toxin
 Causes pathogenesis
 Present only in B.pertussis
 Pertussis toxin is expressed on the
surface, secreted into the surrounding
medium
 Posses Biochemical and Biological activity
of producing lymphocytosis producing
factor causes Lymphocytosis
 Acts as Histamine sensitizing factor
 Islet activating function – causes
excessive Insulin secretion.
Filamentous Hemagglutinin
 One of the Hemagglutinins produced
by B.pertussis
 Filamentous Hemagglutinins adheres
to cilia of the respiratory epithelium
and to erythrocytes
 Helps in binding to respiratory
epithelium
Other Toxins
Adenylate cyclase
 Enters the target cells and acts as
toxin
 It acts by catalyzing the production
of cAmp by various types of cells.
Heat labile Toxin
 Cytoplasmic protein present in
Bordetella
 Dermonecrtoic and lethal in Mice
Tracheal Toxin
 L M W – peptidoglycan
 Causes ciliary damage, produced by
all Bordetella
 It induces ciliary damage in hamster
tracheal ring
 Lipolysacchardie acts as in Gram –
ve bacilli
 Pertactin – OMP produces immunity
in mice.
Variation Smooth to Rough
 B pertussis may alter from smooth to
rough variation
 Phase I to Phase II Phase III Phase
IV( rough stage ) which is rough and
avirulent form
Pathogenicty
 An obligate
parasite
 Intranasal
inoculation in mice
induces a
characteristic
patches and
intensive
pneumonia like In
humans
 Incubation is 1 to 2
Incubation in Whooping cough

 The incubation period (the time


between infection and the onset of
symptoms) for whooping cough is
usually 7 to 10 days, but can be as
long as 21 days.
Stages of Infection

 1Catarrhal
 2Paroxysmal
 3Convalescent
Each stage lasts 2 weeks
Catarrhal stage is Maximal infective
Antibiotics are useful.
Paroxysmal Stage
 Cough increases – distinctive bouts
 Violent spasms of continuous coughing
 With violent act of cough, air enters into
empty lung with characteristic whoop
Enters into next stage
 Leads to convalescence
 And severity of cough decreases
 Total disease lasts for 6- 8 weeks.
Violent Paroxysms of cough
Complications
 The violent bouts of cough leads to
Subconjuctival hemorrhage
Subcutaneous emphysema
Bronchopneumonia
Lung collapse
Neurological complications
Epilepsy, paralysis, mental
retardation, blindness, deafness.
Epidemiology
 Predominately a pediatric disease
 Highest in the 1st year of life
 Maternal antibodies are not protective.
 Females suffers more than males.
 World wide in distribution
 Epidemics occurs periodically.
 In early stage of infection droplets and
fomites contaminated by oropharengeal
secrection are infective.
 Non immune rarely escape infection
Epidemiology
 House hold contacts at risk
 Chronic carriers are not known
 B.pertussis - 95 %
 B.parapertussis – 5%
 B.brochoseptica occasionally occur
 Some times Adenovirus, Mycoplasma
pneumonia may mimics whooping
cough.
Diagnosis
 Isolation by culture
 PCR
 Direct fluorescent antibody
 Serological testing

http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg
How Whooping cough
Diagnosed
 Since the early symptoms are so
non-specific, pertussis is usually not
diagnosed until the appearance of
the characteristic cough. Pertussis
can be confirmed by taking cultures
of respiratory fluids for examination
in the laboratory. This involves
taking a sample of secretions from
the nose or throat and identifying the
pertussis bacteria in the secretion
Laboratory Diagnosis
 Microscopy
 Culture.
 Microscopy – Demonostration of
Bacilli in respiratory secretions.
 Florescent Antibody methods
Cough Plate Method
 Culture plate held at 10-15 cm
infront of the mouth when the
patient is coughing spontaneously or
induced cough
 Droplets of respiratory exhaled
impinge on the media.
 Helpful as bed side investigation
Cough Plate Method
Nasopharyngeal Swab
 Secretion from the
posterior
pharyngeal wall are
collected with
cotton swab on a
bent wire passed
from the oral
cavity
 A West’s post nasal
swab is used for
collection of
specimen.
Per nasal Swab
 Swab on a flexible
wire is passed
along the floor of
the nasal cavity
and material
collected from
Pharyngeal wall
 Dacron or Calcium
alginate swabs are
better
Transport Medium
 Transferred in o
Casamio acid
solution at pH 7.2
in modified Stuarts
medium Glycerin
potato blood agar
of Bordet Gengou
 Adding Pencillin
becomes more
selective
Identification of bacteria
 The culture plates
are incubated at
360c
 The bacteria are
identified by
Microscopy and
slide agglutination
 Immunofluorescen
ce methods
Serology
 Paired serum sample for detection of
antibodies
 Gel precipitation testing
 Complement fixation test
 Detection of Ig A by ELISA from
nasopharyngeal secretions.
Early Immunization is best
solution to prevent the Pertussis
How Whooping Prevented
 Pertussis can be
prevented by the
pertussis vaccine,
which is part of the
DTaP (diphtheria,
tetanus, a cellular
pertussis) vaccine.
These important
immunizations are
routinely given in five
doses before a child's
sixth birthday.
Prophylaxis

 Alum absorbed vaccine is better


 Administered in combination with
Diptheria, and tetanus toxoid
 B pertussis acts as an adjuvant
 Early immunization, is essential in
prevention of infection.
 Later doses are given at the interval
of 4 – 6 weeks intervals, before 6
moths 3 doses are completed.
Booster doses
 A booster at the end of the 1st year
 Another dose at 4th year
 Chemoprophylaxis with Erythromycin when
exposed to contacts in the vicinity

 Complications with vaccination


Post vaccinial encephalopathy
5 – 10 million doses
Neurotic complications
Stop further vaccination
Do not vaccinate after 7 years
Advantages of Acellular Vaccine
 An acellular vaccine containing whole
antigen has been developed and found to
elicit good antibody response with fewer
side effects. It has replaced the classical
vaccine in Japan since 1981 with success,
with fewer out breaks and less side
effects. whooping cough vaccine can be
made from various components of the
Bordetella pertussis bacterium, rather than
the whole organism. This "acellular"
vaccine works well but has fewer side
effects than the traditional "whole cell"
version.
Acellular Vaccines
 Contain the Pertussis bacilli
 Contain PT FHA Agglutinogens 1, 2, 3
 Produces immunity in 90 % of
individuals
 Immunity in only 50 % by 12th year
Treatment
 Pencillin is not useful
 10 days of Erythromycin is useful in
early infection
 Chloramphenicol and Cotrimoxazole
are effective.
B.parapertussis

 Less common
 B.pertussis Vaccine not useful
 Infrequent cause of whooping cough
B.brochiseptica
 A motile pathogen
 Small proportion of cases 0.1% occur
with cough.
 It is antigenically related to
B.pertussis, and Brucella.
Created for Benefit of
Medical and Paramedical
Students in Developing
World.
Dr.T.V.Rao MD
Email
doctortvrao@gmail.com