LECTURE Flashcards
first isolated by Pfeiffer in 1890; waserroneously named during the influenza pandemic that ravaged the world from 1889 to 1890
Haemophilus influenzae
The basis for this assumption was the frequent isolation of this bacillus from the [?] of patients with influenza and from [?] during those times when viral isolation methods were unavailable.
nasopharynx; postmortem lung cultures
secondary (opportunistic) invader
H. influenzae
Influenza, commonly referred to as the flu is a viral disease characterized by [?] of the upper airways.
acute infammation
intense infammation of the mucous membranes lining the nose
(coryza)
severe generalized muscle pain
(myalgias)
require special nutrients for isolation and identification
fastidious
special nutrients that are often supplied by addition of enrichment ingredients to culture media
growth factors
Species in the genus Haemophilus require [?] for optimal growth
Factor X and/or Factor V
Bordetella species, on the other hand, require
niacin (also known as nicotinic acid, a form ofvitamin B3), cysteine, and usually methionine.
Brucella species require
thiamine, niacin, and biotin.
Most bacteria included in this group are [?] or produce [?] infections.
nonpathogenic
opportunistic
General Characteristics
•Small, pleomorphic, gram-negative bacilli. The cells are typically coccobacillary or short rods.
•Nonmotile.
•Facultative anaerobes.
•Growth is enhanced in a 5% to 10% CO2-enriched atmosphere. •Are “blood-loving”
Haemophilus species
requiring enriched media, usually containing blood or its derivatives, that provide preformed growth factors, X and V; isolation usually requires the presence of X and/or V factor in the culture medium.
blood-loving
- Protoporphyrin IX which acts physiologically as hemin or hematin
Factor X
- An important component of cytochromes, catalase, and peroxidase.
Factor X
- Heat-stable and is frequently supplied by the incorporation of heat-lysed (“chocolatized”) blood cells in agar such as in chocolate agar or Fildes medium.
Factor X
- Nicotinamide adenine dinucleotide (NAD) or NAD phosphate (NADP).
Factor V
- Heat-labile and is commonly supplied by the incorporation of yeast extract or other appropriate supplements in the medium
Factor V
- May also be provided by a suspension of hemolytic strains of bacteria (e.g., staphylococci, pneumococci, and neisseriae)
Factor V
Pfeiffer’s bacillus
Haemophilus influenzae
Haemophilus influenzae: CHARACTERISTIC
Requires both X and V factor for growth
Haemophilus influenzae: HABITAT
- only in humans
- upper respiratory tract (oropharynx and nasopharynx) of 20% to 80% of healthy persons
Haemophilus influenzae: TRANSMISSION
person- to-person by respiratory droplets
Strains of H. influenzae are divided into 2 broad groups based on
capsular polysaccharides
These are encapsulated strains of H. influenzae which are separated into one of six groups: type a, b, c, d, e, or f; all have potential to invade deeper tissues.
Typeable strains
90% of invasive H. influenzae infections are caused by .
serotype b (Hib) strains
Haemophilus influenzae [?] is most commonly encountered in serious infections in humans which include meningitis esp. in
infants and children; and several other diseases such as epiglottitis and bacteremia.
serotype b (Hib) strains
They do not produce capsule.
Nontypeable strains
These are most commonly encountered as normal inhabitants of the upper respiratory tract of man; but
may cause mild localized infections (otitis media and sinusitis in children), and is associated with respiratory
tract infections (pneumonia).
Nontypeable strains
Until the availability of the Hib vaccine, H. influenzae was the most common cause of meningitis in children between [?] of age when nearly all passive immunity has waned, and the child enters a vulnerable non immune period of life. Although, it is still a problem if a child is [?] and not vaccinated.
3 months and 6 years
<2 years
Older children, adolescents and adults can less frequently be infected particularly those who are immunocompromised.
Meningitis
Meningitis by H. influenzae has very similar presentation with [?], with symptoms of fever, malaise, occasionally vomiting, stiff neck and neurological impairment. Untreated cases have [?] (up to 90%) even with prompt diagnosis.
meningococcal meningitis
high fatality
H. influenzae is the most common cause of this potentially fatal disease in children between the ages of 2 and 4
Epiglottitis
It has a rapid onset, with sore throat, dysphagia, fever, and swollen, cherry red epiglottis above the larynx at the base of the tongue.
Epiglottitis
Acute inflammation and intense edema of the epiglottis may cause complete [?] and [?]
airway obstruction and suffocation
can be “cherry red” in children; “thumb sign” on lateral neck x-ray
Epiglottitis
is an early manifestation of acute H. influenzae type b meningitis but in some infants, may occur without meningitis
Bacteremia
It is mostly seen in children with underlying diseases (e.g., sickle cell); signs and symptoms include fever, lethargy and high neutrophil count
Bacteremia
are second to S.pneumoniae as a common cause of otitis media in children, most frequently in children aged 6 months to 5 years with highest incidence among children less than 3 years of age
H. influenzae (nontypeable strains)
Signs and symptoms include fever, irritability, headache, occasionally nausea and vomiting, ear pain, hearing loss, discharge from the ear.
Otitis media
It is characterized by persistent cold symptoms, purulent nasal or post nasal discharge, cough, fever, headache, and often facial pain.
Sinusitis
In adults, H. influenzae causes pneumonia, particularly in individuals with other underlying pulmonary infections. It can be a manifestation of systemic infections caused by H. Influenzae type b.
Pneumonia
— lobar, segmental and purulent pneumonia.
pneumococcal pneumonia
Its characteristics are similar to pneumococcal pneumonia
Pneumonia
Hib capsule is a polysaccharide, called PRP
polyribosylribitol phosphate
It is the most important factor of H. influenzae because it allows the organism to resist phagocytosis and intracellular killing by neutrophils and the complement.
Capsule
This molecule consists of the 5-carbon monosaccharide ribose, linked by an ester bond to ribitol, and a 5-carbon sugar alcohol, which, in turn, is linked to a phosphate group.
polyribosylribitol phosphate
the only capsular type that contains two pentose monosaccharides rather than hexose sugars as subunit carbohydrates.
H. influenzae serotype b polysaccharide
promotes phagocytosis and complement-mediated bacteriolysis.
Anticapsular (anti-b) antibodies
H. influenzae is the only member of the genus that produces [?], an enzyme that cleaves secretory IgA present on human mucosal surfaces of the respiratory tract, thus allowing the bacteria to attach to these surfaces.
IgA protease
They favor attachment of the nontypeable strain of H. influenzae to host epithelial cells.
Pili
Each component is responsible for invasiveness, attachment, and antiphagocytic function.
Outer Membrane Proteins
of H. inluenzae has been shown to have a paralyzing effect on the sweeping motion of ciliated respiratory epithelium.
LPS
Antibodies directed against these antigens may play a significant role in human immunity.
Outer Membrane Proteins
Organisms attach to epithelial cells using [?] and [?]
pili and outer membrane proteins (OMP)
Invasion takes place between cells by disruption of [?]. In the submucosa, the [?]allows the bacteria to evade phagocytosis and enter the bloodstream
cell–cell adhesion molecules
capsule
H. influenzae type b (Hib) disease: PREVENTION
vaccination
PRP, like most bacterial polysaccharides, elicits a strong [?], but with little induction of memory.
primary antibody response
[?], which covalently link the polysaccharide to a protein, induce memory type antibody responses in children and are effective in younger infants who are at higher risk for the disease
H. influenzae type b (Hib) conjugate vaccines
PRP-OMPC
PRP-T
PRP-D
HbOC
Neisseria meningitidis outer membrane protein complex
Tetanus toxoid
Diphtheria toxoid
CRM197 mutant Corynebacterium diphtheriae toxin protein
• Hib conjugate vaccines are commercially available as:
‣ Monovalent vaccine
‣ Combination vaccine
(containing a single antigen only — Hib PRP)
‣ Monovalent vaccine
(consists of two or more vaccines given in one
shot — Diphtheria, Pertussis, Tetanus, HBV, Hib)
‣ Combination vaccine
• Depending on which vaccine product is chosen, the series consists of three doses at [?] of age or two doses given at [?] of age. An additional booster dose is given sometime between 12 and 15 months of age.
2, 4, and 6 months
2 and 4 months
It is commonly known as Koch-Weeks bacillus.
Haemophilus aegyptius
H. aegyptius was observed by Koch in 1883 in Egyptians in [?]—hence the species name.
conjunctivitis exudates
The etiologic agent of an acute, communicable conjunctivitis, sometimes called “pink eye”.
Haemophilus aegyptius
was recognized as the causative agent of a severe illness called Brazilian Purpuric Fever (BFP) which originated in Sao Paulo, Brazil in the 1980s.
H. aegyptius biotype III
The illness is characterized by a high fever, abdominal pain with vomiting, a petechial/ purpuric rash, hypotensive shock, and vascular collapse.
Brazilian Purpuric Fever
mortality rate may reach 70% within 48 hours after onset.
Brazilian Purpuric Fever
The growth conditions for this organism are the same as those for H. influenzae
Haemophilus aegyptius
Requires Factor X an Factor V for growth.
Haemophilus aegyptius
It is strictly a human pathogen, infecting the mucosal
epithelium, genital and nongenital skin, and regional
lymph nodes, and spread by sexual transmission.
Haemophilus ducreyi
highly communicable sexually transmitted genital ulcer disease (GUD); soft chancre
chancroid
After an incubation period of
approximately 4 to 14 days, a nonindurated, painful lesion with an irregular edge develops, generally on the genitalia or perianal areas accompanied by suppurative, enlarged and painful inguinal lymph nodes
chancroid
The disease must be differentiated from syphilis, herpese simplex infection, and lymphogranuloma venereum.
chancroid
pale-staining, gram-negative coccobacilli, often arranged in clustered groups (“school of fish”) or loosely coiled parallel chains (“railroad tracks”) - rarely seen in clinical specimens
Haemophilus ducreyi
Organisms may be inside and outside of polymorphonuclear leukocytes (PMNs).
Haemophilus ducreyi
The organism is more fastidious than H. influenzae.
Haemophilus ducreyi
Requires X factor for growth.
Haemophilus ducreyi
may be difficult to recover in culture as it requires additional growth factors and special media for cultivation in the laboratory
Haemophilus ducreyi
(1) [?] supplemented with 5% chocolatized horse blood plus 1% IsoVitalex enrichment.
(2) [?]supplemented with 2% bovine hemoglobin, 5% fetal calf serum, and 1% IsoVitalex.
Müeller–Hinton agar
GC agar base
[?] (3 µL/mL final concentration) may be added to inhibit contaminating gram-positive bacteria
colonizing the genital tract. Certain strains of H. ducreyi have shown to be sensitive to this antibiotic; using more than one media type to optimize the recovery of H. ducreyi may be necessary.
Vancomycin
Cultures for H. ducreyi should be incubated at [?] in 5% to 10% CO2 in a candle jar or CO2 incubator with high humidity; most produce visible growth in 2 to 4 days, but may require for as long as 7 days to grow.
33°C
• It is a member of the normal oral and nasopharyngeal flora.
Haemophilus parainfluenzae
• It is involved in infective endocarditis in adults with underlying congenital or rheumatic heart disease which is characterized to have an insidious onset. Symptoms first appear approximately 1 month after routine dental procedures and primarily involves the mitral valve.
Haemophilus parainfluenzae
• Requires V factor for growth.
Haemophilus parainfluenzae
• They are are part of the normal flora of the respiratory tract and are rarely associated with infections.
Haemophilus haemolyticus and Haemophilus parahaemolyticus
Nonencapsulated strains are (1-2 mm)
smooth, blue-gray in color and translucent at
24 hours; encapsulated strains form larger,
more mucoid colonies; mouse nest odor.
H. influenzae
Resembles H. influenzae, except colonies are
smaller at 48 hours.
H. aegyptius
On selective medium: Small, flat, smooth,
and translucent to opaque at 48-72 hours;
colonies can be pushed intact across agar
surface.
H. ducreyi
Medium to large, smooth, light gray, and
translucent.
H. parainfluenzae
Resembles H. influenzae
H. haemolyticus
Resembles H. parainfluenzae.
H. parahaemolyticus
The genus Bordetella includes three primary human pathogens:
Bordetella pertussis
Bordetella parapertussis
Bordetella bronchiseptica
• Small, gram-negative coccobacilli on primary isolation.
- On subculture, they tend to become more pleomorphic.
• Obligately aerobic.
• Grow optimally at 35°C to 37°C
• Catalase (+)
• Do not utilize carbohydrates.
• Relatively inactive in biochemical test systems
Bordetella species
• Bordet-Gengou bacillus
Bordetella pertussis
strictly human pathogen that colonizes the cilia of the
respiratory epithelium
Bordetella pertussis
Vaccinated individuals serve as reservoir.
Bordetella pertussis
transmitted by direct contact with respiratory droplets or by inhalation of infectious aerosols
Bordetella pertussis
a contagious childhood illness that causes an acute tracheobronchitis, with a 7-10 day incubation
Pertussis or whooping cough
Pertussis or whooping cough follows a prolonged course consisting of three overlapping stages
(1) Catarrhal phase
(2) Paroxysmal phase
(3) Convalescent phase
- The onset is insidious and persists for 1-2 weeks; it is so named because of mucous membrane inflammation (catarrh).
Catarrhal phase
Symptoms are nonspecific, resembling common colds, and include sneezing, mild cough, runny nose, and perhaps conjunctivitis, although infants can develop apnea or respiratory distress or both.
Catarrhal phase
- At this stage, the infection is highly communicable because of the large number of organisms in the upper respiratory tract and cause of disease is unrecognized.
Catarrhal phase
This begins during the second week of illness and is characterized by paroxysms of cough (severe, repetitive coughing) followed by the characteristic “whoop”. The whooping sound is caused by the rapid gasp for air following the prolonged bout of coughing.
Paroxysmal phase
Coughing spells may occur many times a day and often every few minutes, and are sometimes followed by vomiting. This lasts for 2-4 weeks.
Paroxysmal phase
Generally begins within 4 weeks of onset with a decrease in frequency and severity of the coughing spells. Gradual recovery occurs over weeks or months.
Convalescent phase
Pneumonia (due to B. pertussis or other bacterial pathogens), otitis media, and encephalopathy are among the secondary complications.
Convalescent phase
Mediate adhesion of the organism to ciliated epithelial cells and are essential for tracheal colonization
Fimbriae; Filamentous hemagglutinin (FHA); and Pertactin
major virulence factor of B. pertussis
Pertussis toxin (PT)
an A-B toxin characterized as a protein exotoxin found outside of the B. pertussis cell.
Pertussis toxin (PT)
is internalized and ADPribosylates a G protein that affects adenylate cyclase activity.
A subunit (enzymatic subunit)
mediate attachment of the toxin to carbohydrate moieties on the host cell surface.
B subunit (binding subunit)
The main activity of PT is modification of host proteins by adenosine diphosphate-ribosyl transferase, which interferes with signal transduction, others are promotion of lymphocytosis, sensitization to histamine, and enhanced insulin secretion (insulinemia).
Pertussis toxin (PT)
It is a fragment of the bacterial peptidoglycan that inhibits DNA synthesis in ciliated cells of the upper respiratory tract.
Tracheal cytotoxin
appears to act in concert with endotoxin (LPS) to induce nitric oxide, which kills the ciliated epithelial cells
Tracheal cytotoxin
It is a potent, pore-forming toxin which enters the host cells and catalyzes the conversion of ATP to cyclic AMP at level far above what can be achieved by normal mechanisms.
Adenylate cyclase (AC)
This activity interferes with cellular signaling, chemotaxis, superoxide generation, and function of immune effector cells, including PMNs, lymphocytes, macrophages, and dendritic cells.
Adenylate cyclase (AC)
can also induce programmed cell death (apoptosis).
Adenylate cyclase (AC)
Whooping cough is preventable by
vaccination
that contain combinations of virulence factors have been licensed for use
Acellular pertussis vaccines
All contain PT and FHA, and pertactin or pili in some. In combination with [?], the acellular vaccine has now replaced the whole cell DTP as DTaP (“a” for acellular).
diphtheria and tetanus toxoids
Every infant should receive three injections of [?] during the first year of life (at 2, 4, and 6 months) followed by a booster series (at 15-18 months, 4-6 years) for a total of five doses.
pertussis vaccine
It may produce a disease similar to whooping cough, but it is generally less severe. The infection is often subclinical.
Bordetella parapertussis
Is said to have a silent copy of the pertussis toxin gene
Bordetella parapertussis
It is a respiratory tract pathogen of numerous animals, including dogs, in which it causes kennel cough; rabbits in which it causes snuffles; and swine causing atrophic rhinitis
Bordetella bronchiseptica
It is infrequently responsible for chronic respiratory tract infections in humans which generally manifest with a nonspecific cough or bronchitis, primarily in individuals with underlying diseases.
Bordetella bronchiseptica
Similar with B. parapertussis; has a silent copy of the pertussis toxin gene. This organism also possesses a β-lactamase that renders it resistant to penicillins and cephalosporins.
Bordetella bronchiseptica
cause disease primarily in domestic, and some wild animals
Brucella
In animals, they typically have predilection for organs rich in erythritol present in the reproductive organs, and sterility or abortion are often the only signs of the disorder.
Brucella
represents a potent localizing factor in the relevant species, but is absent in humans.
Erythritol
is either an acute febrile disease or a persistent disease with a wide variety of symptoms.
Human brucellosis
Because of their potential application in bioterrorism, Brucella species are considered [?] select biological agents by the CDC. These agents are easy to disseminate and cause moderate morbidity but low mortality
category B
• Gram-negative (but often stain irregularly) coccobacilli or short bacilli, 1.2 µm in length.
• Nonmotile
• Non-spore-forming.
• Aerobic. ( Whereas B. abortus requires 5–10% CO2 for growth).
• Have complex nutritional requirements - been cultivated on defined media
containing amino acids, vitamins, salts, and glucose.
• Catalase (+)
• Oxidase (+)
• Urease (+)
• Nitrate(+)
Brucella species
- Brucella melitensis -
- Brucella suis -
- Brucella abortus (Bang’s bacillus) -
- Brucella canis -
goats and sheep
swine
cattle
dogs
most important source of Brucella infection in humans.
Brucella melitensis
are transmitted to humans from infected animals or contaminated animal products
Brucella species
The organisms may gain entry into the body through a variety of portals.
Brucella species
Brucella species: Transmission
Oral entry, by [?] of contaminated animal products (often raw milk or its derivatives) or by [?] with contaminated fingers.
ingestion
contact
Brucella species: Transmission
[?] containing the bacteria
[?] of the conjunctivae
Inhalation of aerosols
aerosol contamination
Brucella species: Transmission
[?] through skin abrasions or by accidental inoculation
Percutaneous infection
Human infections with Brucella species are associated predominantly with [?] in slaughterhouses, livestock handling, and veterinary trade.
occupational contact
Human-to-human transmission, although rare, may occur through [?] and [?]
sexual contact and breast-feeding
Malta fever
undulant fever
Bang’s (after B.L. Bang, a Danish physician) disease
Brucellosis
are facultative intracellular pathogens, multiplying mainly in monocyte-macrophage cells.
Brucellae
Brucellae are carried to the regional lymph nodes through the lymphatic fluid.
Brucellosis
Phagocytes infected with brucellae are released into the bloodstream and are lodged into organs creating focal lesions in liver, spleen, bone marrow, and kidney.
Brucellosis
3 stages of brucellosis based on disease duration
(1) Acute
(2) Subchronic or Undulant
(3) Chronic
Is marked by non-specific symptoms including fever,
malaise, headache, anorexia, arthralgia, myalgia, and
back pain that usually become apparent within 1 to 4
weeks of exposure
Acute
Typically occurs within a year of exposure and is
characterized by undulating fevers (body temperatures that rise in the afternoon and evening and fall in the morning), arthritis, and epididymoorchitis (inflammation of the epididymis and testis).
Subchronic or Undulant
Commonly manifests 1 year after exposure with symptoms, such as depression, arthritis, and chronic fatigue syndrome.
Chronic
The brucellae that infect humans have apparent
differences in
pathogenicity
usually causes mild disease without suppurative complications; noncaseating granulomas of the reticuloendothelial system are found
B. abortus
also causes mild disease
B. canis
infection tends to be chronic with suppurative lesions; caseating granulomas may be present
B. suis
infection is more acute and severe
B. melitensis
Ability to survive and multiply within professional phagocyte - facilitated by inhibition of both the [?] and of [?]
myeloperoxidase system
phagosome–lysosome fusion
- prolongs the life of the host cell where the brucellae are replicating.
Inhibition of apoptosis
Prevention is primarily by measures that minimize [?] and by the [?] of dairy products.
occupational exposure
pasteurization
Control of brucellosis rests on limitation of spread in animals which involves a combination of [?] with an attenuated strain of B. abortus and [?] of infected stock.
immunization
eradication
No human vaccine is in use
Brucellae
