BORDETELLA AND HAEMOPHILUS
MBIM 650/720 Medical
know the general morphology and physiology the organisms
know epidemiology and clinical symptoms
understand the mechanisms pathogenesis
know the diagnostic, therapeutic and preventive procedures
READING: Murray, et
al.: Medical Microbiology, 3rd ed., Chapter 33, pp. 265-269 and
chapter 34, pp. 276-281
is the only organism of major clinical significance, causing whooping
cough in infants and young children. However, a closely related
organism, B. parapertussis can also cause a milder form of
bronchitis. B. bronchosepticus, another member of the genus Bordetella,
is the causative agent of respiratory diseases in cats and swine, but
can cause broncho-pulmonary symptoms in severely immunosupressed
BLOOD LYMPHOCYTOSIS IN A PATIENT WITH
PERTUSSIS. The lymphocytes in this blood smear from an
18-month-old child with a Bordetella pertussis infection
have lobulated nuclei. Lymphocytosis is characteristic
of this disorder and the lymphocyte morphology is often
atypical. The cytology of the cells could be mistaken
for neoplastic lymphocytes. (Wright-Giemsa stain) ©
The Johns Hopkins Autopsy Resource (JHAR). Image Archive.
is an extremely small, strictly aerobic, Gram negative, non-motile
cocobacillus (short rod). Compared to other Bortdetella species, B.
pertussis does not grow on common laboratory media and can be
distinguished from B. parapertussis in that B. pertussis
is oxidase positive but urease negative, while B. parapertussis
is oxidase negative and urease positive. B. bronchosepticus is
positive for both enzymes.
Pertussis in the US, 1940-1999 CDC
This child has pertussis. It is difficult for him to stop
coughing and to get air. Coughing spasms with a
"whooping" sound that follows the cough are typical.
The sound means child is trying to catch his breath before the
next round of coughing WHO
Most of the patients
with whooping cough are less than a year old although older children may
also get the disease. The severity of disease is also age-related. The
organism, contained in aerosol droplets, gains access via inhalation and
colonizes the bronchial ciliary epithelial cells. After a week to 10
days of incubation period, mild symptoms of rhinitis, mild cough and
sneezing occur (catarrhal stage) which last 1-2 weeks. Further
proliferation of the organism compromise ciliary function and is
accompanied by increased frequency and intensity of symptoms. This leads
to the paroxysmal stage, characterized by paroxysms of cough
followed by a prolonged and distressing inspiratory gasp (whoop). The
cough, which recurs at variable intervals and often every few minutes,
may last for 2-3 weeks. The cough interferes with oral intake, and the
swallowed mucus may induce vomiting, resulting in severe dehydration and
weight loss. Hypoxia during prolonged attacks may lead to seizure,
hypoxic encephalopathy or coma. The cough episodes slowly decrease and
there is gradual recovery over 3-16 weeks (convalescent stage).
Pneumonia (due to B. pertussis or other bacterial pathogens),
otitis media, rectal prolapse and meningo-encephalitis are among the
following the infection are due to many factors. In addition to the
attachment to and growth on ciliated cells, the organism produces a
number of exotoxins
which contribute to these symptoms.
Pertussis toxin is
an oligopeptide AB-type exotoxin that is the major cause of pertussis
(abnormal cough). It causes T cell lymphocytosis
and has adjuvant
properties. It also causes hypoglycemia, increased IgE synthesis, and
increased histamine and endotoxin
sensitivity. The organism inhibits many leukocyte functions, including chemotaxis,
phagocytosis and respiratory burst and impairs NK cell killing. It also
contributes to bacterial binding to ciliated epithelial cells. It exerts
many of its effects by covalent addition of ADP-ribose to the GTP
binding Gi protein and thereby preventing the deactivation of adenylate
cyclase. This results in the accumulation of large amounts of cAMP which
leads to increased mucus secretion and interferes with many cellular
Binding of pertussis toxin to cell membrane
penetrates the host cells, is activated by calmodulin
and catalyzes the conversion of ATP to cAMP. Like pertussigen, it also
inhibits phagocyte and NK cell functions. However, in contrast with
pertussigen, the cAMP increase caused by this toxin is short-lived.
This is a
peptidoglycan-like molecule (monomer) which binds to ciliated epithelial
cells, thus interfering with ciliary movement. In higher concentrations,
it causes ciliated epithelial cell extrusion and destruction. The
destruction of these cells contributes to pertussis.
is a very strong vaso-constrictor and causes ischemia and extravasation
of leukocytes and, in association with tracheal cytotoxin, causes
necrosis of the tracheal tissue.
These are not
exotoxins but are filament-associated lipo-oligo-saccharides which are
implicated in the binding of the organism to ciliated epithelial cells.
Antibodies against these molecules are protective, probably by
preventing bacterial attachment.
Like LPS of
other gram negative bacteria, these endotoxins cause a number of
patho-physiolocigal effects. When released in relatively large
quantities following bacterial cell lysis, they cause irreversible shock
and cardiovascular collapse. In smaller quantities, they activate a
variety of inflammatory mediators ( TNF, IL1, IL6, prostaglandins, etc.)
and generate complement activation products.
characteristic. Laboratory diagnosis is made by obtaining a
nasopharyngeal aspirate and primary culture on Bordet-Gengou medium
(potato-glycerol-blood agar). Growth is inhibited by peptones,
unsaturated fatty acids, sulphides, etc. found in ordinary media.
The organism grows as small transparent hemolytic colonies. It can be
serologically distinguished from B. parapertussis and B.
A killed whole
bacterial vaccine is normally administered as DPT combination. An
acellular vaccine consisting of filamentous hemagglutinins and
detoxified pertussigen is also available and is recommended for booster
shots. Erythromycin is the current drug of choice.
The genus Haemophilus
contains many species but H. influenzae is the most common
pathogen. Other species of Haemophilus that are of clinical
importance to immuno-competent humans are H. ducreyi (causes chancroid:
an STD), H. influenzae aegyptius (associated with conjunctivitis
and Brazilian purpuric fever) and H. parainfluenzae (a rare cause
of pneumonia and endocarditis).
There are several species of Hemophilus that are normal flora,
but may be pathogenic in immuno-compromised hosts. The capsulated strain
of H. influenzae (type b) is most virulent, although some
non-encapsulated (non typable) strains are also pathogenic.
Incidence of H. influenzae non-type b invasive disease among children
<5 years of age, 1996. CDC/Barbara Rice email@example.com
- coccobacillus prokaryote (dividing); causes meningitis in children,
pneumonia, epiglottitis, laryngitis, conjunctivitis, neonatal infection,
otitis media (middle ear infection) and sinusitis in adults (SEM x
64,000) © Dr
Dennis Kunkel, University of Hawaii. Used with permission
is a small Gram negative bacillus which can be grown on chocolate agar
(heated blood) and requires hemin (factor X) and nicotinamide adenine
dinucleotide (NAD+:factor V) for growth which is enhanced by
high CO2 concentration (5%). It does not grow on normal blood
agar. The factor V and factor X requirement can be used to distinguish
between H. influenzae which requires both, H. parainfluenzae
which requires factor V only and H. ducreyi which requires factor
X only. H. influenzae are divided into several strains on the
basis of capsular polysaccharides (a-f) or the absence of a capsule
Clinical symptoms of infection by Haemophilus
This child has swollen face due to Hib infection. The
tissue under the skin covering the jaw and cheek is infected.
Infection is spreading into her face. She is probably very
sick Courtesy of Children's Immunization Project,
St. Paul, MN
Gross pathology of subacute bacterial endocarditis
involving mitral valve. Left ventricle of heart has been
opened to show mitral valve fibrin vegetations due to
infection with Haemophilus parainfluenzae. Autopsy. CDC/Dr.
Edwin P. Ewing, Jr. firstname.lastname@example.org
causes a variety of clinical symptoms some of which may depend on the
presence of the bacterial capsule. Until the availability of the Hib
vaccine, the type-b H. influenzae was the main cause of
meningitis in children between 6 months and 5 years, although older
children, adolescents and adults can also be infected. The infection
initially causes a runny nose, low grade fever and headache (1-3 days).
Due to its invasive nature the organism enters the circulation and
crosses the blood-brain barrier, resulting in a rapidly progressing
meningitis (stiff neck), convulsions, coma and death. Timely treatment
may prevent coma and death, but the patient may still suffer from
deafness and mental retardation. Type-b H. influenzae may also
cause septic arthritis conjunctivitis, cellulitis,
the latter results in the obstruction of the upper airway and
suffocation. H. influenzae of other types may rarely cause some
of the symptoms listed above. Non-typable strains of H. influenzae
are the second commonest cause of otitis
media in young children (second to Streptococcus pneumoniae).
In adults, these organisms cause pneumonia, particularly in individuals
with other underlying pulmonary infections. These organisms also cause
acute or chronic sinusitis in individuals of all ages.
mechanism of pathogenesis is not known but the presence of capsule,
which is anti-phagocytic, is a major factor in virulence. Type-b H.
influenzae are more invasive and pathogenic than other strains. The
lipopolysaccharide is responsible for the inflammatory process. The
organisms also produce IgA1-specific protease which may aid their
diagnosis is based on history, physical examination and symptoms. Blood
cultures are positive in more than 50% of symptomatic patients, except
those with conjunctivitis. Polyribitol phosphate (PRP), a component of
the capsular polysaccharide is present in the serum, cerebrospinal fluid
(CSF) and concentrated urine of more than 95% of H. influenzae-b
meningitis cases. Gram-negative cocobacilli can be found in the CSF in
more than 80% of meningitis cases. Some Gram-stained preparations may be
useful in rapid diagnosis of septic arthritis and lower respiratory
treatment is initiated, H. influenzae-b meningitis and
epiglotitis are almost 100% fatal. Due to common resistance to
ampicillin and some resistance to chloramphenicol, cephalosporin, which
penetrates the blood brain barrier, is the antibiotic of choice in these
cases. Other diseases caused by this organism can be treated with
ampicillin (if susceptible) or choice of trimethoprim-sulphamethoxazol,
tetracyclin and cefaclor.
Countries implementing routine childhood Hib immunization WHO
Hib-C vaccine which
consists of capsular PRP conjugated to tetanus toxoid has been used
successfully to provide protection and is a part of the recommended
routine vaccination schedule.
This is a
significant cause of genital ulcers (chancroid)
in Asia and Africa but, is seen less commonly in the United States. The
incidence is approximately 4000-5000 per year with clusters found in
California, Florida, Georgia and New York. The infection is asymptomatic
in women but about a week following sexual transmission to a man, it
causes appearance of a tender papule with erythematous base on the
genitalia or the peripheral area. The lesion progresses to become a
painful ulcer with inguinal lymphadenopathy. The H. ducreyi
lesion (chancroid) is distinguished from a syphilitic lesion (chancre)
in that it is a comparatively soft lesion. The organism is more
fastidious than H. influenzae but can be grown on chocolate agar,
supplemented with IsovitaleX in 5%-10% CO2 atmosphere and the
growth can be detected in 2-4 days.
previously known as H. aegyptius, causes an opportunistic
organism which can result in a fulminant pediatric disease (Brazilian
purpuric fever) characterized by an initial conjunctivitis, followed by
an acute onset of fever, accompanied by vomiting and abdominal pain.
Subsequently, the patient develops petechiae,
shock and may face death. The pathogenesis of this infection is poorly
understood. The growth conditions for this organism are the same as
those for H. influenzae.
Both H. ducreyi
and H. influenzae aegyptius can be treated with erythromycin.