Micro-O Haemophilus And Bordetella

Front 1

until recently, this organism was the most common cause of bacterial meningitis in children < 4 years

Back 1

Haemophilus influenzae (type b)
(Hib) affected 41 per 100,000 children under 5 in 1987, only 1.3 per 100,000 in 1998

Front 2

What percentage of children infected with Hib developed meningitis?

What was mortality due to this diease?

Back 2

60% developed meningitis

death rate due to this disease is 3-6%

Front 3

Basic morphology, staining characteristics of Haemophilus influenzae

Back 3

small, gram (-)
non-motile, non-spore-forming baccilus (or coccobacillus) with complex nutritional requirements (FASTIDIOUS)

Front 4

Pathogenesis of Hib

Back 4

-natural disease only in humans
-no known exotoxin, endotoxin not significant in pathogenicity, anti-capsular Abs are protective
-produces IgA protease

Front 5

Hib transmission

Back 5

respiratory aerosols between children

Front 6

carrier rate of Hib in children may be:

Back 6

30-50% (who may harbor unencapsulated strains)

Front 7

disease caused by Hib starts as what?

Back 7

NASOPHARYNGITIS (with otitis media or sinusitis)

BACTEREMIA may follow with involvement of the meninges
(epiglottitis is less common, but equally serious)

Front 8

Hib bacteria infecting nasopharyngitis can spread where?

Back 8

face (cellulitis) or joints (pyarthrosis, pus in joint)

in addition to epiglottitis, otitis media, sinusitis,

Front 9

most serious complications of Hib infection

Back 9

MENINGITIS and EPIGLOTTITIS

Front 10

what is special about the types a-f of H. influenzae

Back 10

possesses an ANTIPHAGOCYTIC polysaccharide capsule,

capsular carbohydrates provoke protective antibodies (capsule is the basis for serotyping)

Front 11

how is type b H. influenzae different from types a, c, d, e, and f?

Back 11

b has a ribose (5 carbon sugar) rather than hexose in its polysaccharide capsular structure
(no known if/how this unusual ring structure relates to the pathogenicity of the type b bacterium)

Front 12

what type of colonies do encapsulated virulent strains of H. influenzae grow?

Back 12

smooth colonies (spontaneously give rise to "rough" unencapsulated variants

Front 13

what is required for Hib growth?

Back 13

this facultative anaerobe requires:
2 growth factors (X (hemin) and V (NAD or NADP)

Front 14

what does Staphylococcus provide for Hib that facilitates its growth?

Back 14

V factor (NAD or NADP) (X & V factors also released from RBCs by the action of the hemolysins secreted by some species of Staph and Streptococci)

Front 15

What will be seen on agar plates of H. influenzae and Staphylococci?

Back 15

staphylococcal colonies will be surrounded by small SATELLITE COLONIES of H. influenzae

Front 16

what type of medium is used to grow Hib?

Back 16

chocolate agar (heated/lysed RBCs release both X and V)

Front 17

are sugar fermentations useful in Hib Dx?

Back 17

NO

Front 18

why do clinical samples of Hib not last for very long?

Back 18

very susceptible to disinfectants and drying

Front 19

Why was Hib particularly harmfum to children under age 4?

Back 19

kids aquire passive immunity from mom that lasts for a few months

after 3 to 4 years, most children aquire active immunity from asymptomatic infection

Front 20

vaccine for Hib

Back 20

conjugate capsular vaccine (1988) effective
vaccine is capsule (PRP) linked to diptheria toxoid so as to have increased dependence of T cells and memory as compared to the previous formulation (only composed of capsule)

2004: version with synthetic carb moiety introduced

Front 21

Dx of Hib

Back 21

Hx and age of patient most important
cultures of blood and spinal fluid
-gram stain (-)
-CSF streaked on chocolate agar, incubated in CO2
-demonstrate requirement for X and V factors
-immunofluorescence or immunoelectrophoreses (to detect tybe b casular Ag) (sometimes latex agglutination test)

Front 22

Treatment for Hib Meningitis

Back 22

AMPICILLIN = drug of choice
(3rd generation cephalosporin used immediately since some isolates amp-resistant)

AUGMENTIN:
ampicillin + clavulanate (a beta-lactamase inhib), for amp-resistant strains)

Front 23

long-term prognosis after recovery from Hib Meningitis

Back 23

if treated early, mortality low

previously 1/3 of those who recovered had residual neuro damage (has been decreased with use of corticosteroids during Ab treatment to reduce inflammation and cytokine production due to LPS released as a result of bacteria lysis)

Front 24

Hib prophylaxis

Back 24

RIFAMPIN (or single dose of ciprofloxacin or cefriaxone)

Front 25

what is non-typeable H. influenzae

Back 25

DOES NOT HAVE polysaccharide CAPSULE
utilized cell-surface adhesions and LPS to colonize cell surfaces
no known role for toxins

Front 26

how is growth and metabolism of non-typeable H. influenzae, different from typeable H. influenzae?

Back 26

IT IS NOT DIFFERENT
(identical to typeable strains)

Front 27

How is pathogenesis of non-typeable H. influenzae different from typable strains?

Back 27

generally non-typeable strains are restricted to the respiratory tract and infections of the ear

Front 28

2nd most common cause of otitis media (after S. pneumoniae)

Back 28

non-typeable H. influenzae

Front 29

why is otitis media caused by non-typeable H. influenzae most common in kids?

Back 29

immune system does not fight off infections of the respiratory tract as effectively

structure of the eustacian tube in young kids has straighter angle and shorter length- more prone to infections

Front 30

non-typeable H. influenzae causes respiratory infections in patients with:

Back 30

underlying respiratory issues (COPD, chronic bronchitis, CF), sinusitis, conjunctivitis and otitis media

Front 31

non-typeable H. influenzae colonization starts in the nasopharynx with preferential adhesion to respiratory mucus, non-ciliated cells and damaged epithelium, what surface structures contribute to adhesion?

Back 31

a) peritrichous pili
b) cell surface adhesions: Hap; Hia; HMW1/2; P2 and P5 porins; OapA OM protein; LPS

Front 32

Hap adhesion is found in what organisms?

Back 32

typeable and non-typeable H. influenzae

Front 33

HMW 1/2 adhesion is expressed by:

Back 33

non-typeable H. influenzae (but not typable) strains

Front 34

Hia adhesion is expressed in:

Back 34

non-typeable H. influenzae strains lacking MHW1/2

Front 35

Hsf: is a homologue of what?
found in what H. influenzae strains?

Back 35

homologue of Hia found in TYPEABLE strains

Front 36

LPS in non-typeable H. influenzae may bind to what receptor?

Back 36

the PAF (platelet activating factor) receptor

Front 37

Invasion of non-typeable H. influenzae (Haemophilus) is thought to occur via what 3 possible mechanisms?

Back 37

a) MACROPINOCYTOSIS (gets cell to engulf it)
b) PARACYTOSIS: passes bt cells to invade sub-epi space (OM protein required)
c) LPS binding to PAF may also facilitate invation

Front 38

What happens post non-typeable H. influenzae invasion?

Back 38

TBA (not yet known)

Front 39

Characteristics of immunity to non-typeable H. influenzae

Back 39

1) passive immunity from mom only lasts a few months
2) adults are susceptible (not clear that long-term immunity develops to non-typeable strains as in Hib)
3) Immunity STRAIN SPECIFIC
4) NO VACCINE currently

Front 40

Dx non-typeable H. influenzae

Back 40

demonstrate requirement for X and V factors
typing is not typically informed, unless isolates are from invasive infections (eg meningitis)

Front 41

Treatment of non-typeable H. influenzae

Back 41

AMOXICILLIN for localized infections (~20-35% of isoaltes are resistant to amoxicillin)
Alternative: AUGMENTIN (amp + beta lactamase inhibitor (clavunate)) or CEFTRIAXONE

Front 42

Why can non-typeable H. influenzae infections be persistent and recurrent?

Back 42

BIOFILMS?
ABILITY TO INVADE HOST CELLS and AVOID Antibiotics?

Front 43

Haemophilus ducreyi

Back 43

emerging STD in US (chanroid = soft chancre, ragged ulcer on genetalia) more common in Africa and Asia

Rx: SULFONOMIDES, TETRACYCLINE and STREPTOMYCIN

Front 44

Haemophilus aegypticus

Back 44

(Koch-Weeks bacillus) produces a purulant conjunctivities, common in hot climates

Front 45

Haemophilus parainfluenzae

Back 45

occasional cause of pharyngitis and bacterial endocarditis

Front 46

the cause of whooping cough

Back 46

Bordetella pertussis

Front 47

Whooping cough characteristics

Back 47

begins with mild upper respiratory symptoms, followed by acute inflammation of trachea, bronchi and bronchioles with a paroxysmal cough, lasting 1-4 weeks

Front 48

general properties of Bordetella pertusis

Back 48

small, gram (-) cocco-bacillus (similar in appearance to H. influenzae
-strict AEROBE
-no requirement for X and V factors (unlike H. influenzae)
-B. pertussis requires VERY FRESH media for growth (so most labs have switched to PCR to detect organism from washes of nasal cavity)
-found only in humans, no known animal reservoir

Front 49

4 Toxins (virulence factors) expressed by Bordetella pertussis

Back 49

a) Pertussis toxin
b) Calmodulin-stimulated adenylate cyclase toxin
c) Dermonecrotic toxin
d) Tracheal cytotoxin

Front 50

Pertussis toxin
(virulence factor expressed by Bordetella pertussis)

Back 50

ADP-ribosylating toxin that catalyzes transfer of ADP-ribobse from NAD to G-proteins in target cells, eg:
-Inhibiting AC, causing ACCUMULATION of cAMP
-affects PLC and ion channels
combined axn causes lymphocytosis, sensitization to histamine, and enhanced insulin secretion

Front 51

Calmodulin-stimualted adenylate cyclase toxin
(virulence factor expressed by Bordetella pertussis)

Back 51

catalyzes the production of cAMP from ATP and is activated by endogenous calmodulin

increased cAMP may impair leukocyte fxn and even cause cell death

Front 52

Dermonecrotic toxin
(virulence factor expressed by Bordetella pertussis)

Back 52

(aka mouse lethal toxin or heat-labile toxin)
causes vascular SM contraction resulting in ischemic necrosis of lung tissue

Front 53

Tracheal cytotoxin
(virulence factor expressed by Bordetella pertussis)

Back 53

causes ciliostasis, inhibits DNA synthesis and ultimately kills tracheal epithelial cells

Front 54

Bacterial colonization by Bordatella pertussis is mediated through several factors:

Back 54

-PILI mediate attachment to ciliated epi cells of upper Resp. tract and decrease ciliary activity
-FHA (pilus-like filamentous humagglutinin)
-PERTACTIN (surface molecule plays role in colonization)
acute local inflammation, + mucous secretions, and patchy ulceration of resp. epi follow. may result in - O2 supply or pneumonia

Front 55

does Bordatella pertusis invade bloodstream?

Back 55

NO

Front 56

How are virulence factors of Bordatella pertussis regulated?

Back 56

expression of genes coding virulence factors is regulated at TRANSCRIPTIONAL level by "TWO COMPONENT" SYSTEM:
transmembrane sensor protein that responds to host environmental cused to phosphorylate a cyto response regulator protein that binds DNA to activate transcription from appropriate promoters

Front 57

Clinical features of Bordatella pertussis:
incubation period:
stages:

Back 57

incubation: 7-10 days
CATARRHAL STAGE: runnin nose, low-grade fever, mild occasional cough
PAROXYSMAL STAGE: bursts of counging, high-pitched "whoop" and occasional vomiting, patients can become cyanotic during cough attacks (more frequent at night) *infants don't WHOOP

Front 58

how has incidence of whooping cough been diminished?

Back 58

IMMUNIZATION 120,000 cases in 1950 to 2000 by 1997

Front 59

why has pertussis not been eliminated?

Back 59

neither immunization nor the disease produces lifelong immunity

old, heat killed vaccine (part of DTP) had potential side effects of encephalopathy and permanant neuro sequelae (led to fewer infants receiving vaccine in 80/90s)

new lower-risk vaccines with specific pertussis antigens (safer and more effective) DTaP

Front 60

how is Bordatella pertussis transmitted?

Back 60

aerosolized droplets during sneezing/coughling (very contagious)

Front 61

what cuases the "Whoop" in whooping cough caused by Bordatella pertussis/

Back 61

inspiration through a narrowed glottis following, long series of coughts

Front 62

Why are infants susceptible to whooping cough?

Back 62

Ab xing placenta not adequate protection for passive immunity

Front 63

when are Abs in children infected with whooping cough found?

Back 63

only several weeks after infection

Front 64

Dx of whooping cough

Back 64

1) Hx of contact, classic cough, marked lymphocytosis
2) Isolation of organism by naso-pharyngeal swab or cough plate, colonies grow slowly. ID by appearance of colony, gram stain (-) biochem rxns. rapid direct fluorescein labeled Ab test for naso-pharyn specimens

Front 65

Antibiotic used for Bordatella Pertussis

Back 65

ERYTHROMYCIN = drug of choice
alternatives: TETRACYLCIN, CHLORAMPHENICOL (not sensitive to penicillin or ampicillin)

Front 66

B. parapertussis can cause what?

Back 66

sporadic cases of whooping cough

(similar virulence factors to B. pertussis, but does not carry gene for pertussis toxin)

Front 67

B. bronchiseptica causes:

Back 67

respiratory illness in animals and only occassionally in humans

(similar virulence factors to B. pertussis, but does not carry gene for pertussis toxin)

Front 68

agent of meningococcal meningitis

Back 68

NEISSERIA MENINGITIDIS
aka MENINGOCOCCUS

Front 69

agent of gonorrhea

Back 69

NEISSERIA GONORRHOEAE (aka gonococcus)

Front 70

common features of MENINGOCOCCUS and GONOCOCCUS

Back 70

1) Gram (-) diplococci
2) Require rich medium for isolation
3) readily killed by drying, heat, disinfectants
4) no known animal reservoir
5) oxidase (+)
6) both ferment GLUCOSE
7) secrete an IgA1 protease
8) Pili and OMPs may contribute to colonization (&morphology on agar)
9) LOS (contains no O side chains, but still endotoxic and mediates resistance to serum bactericidal activity)

Front 71

How can one distinguish MENINGOCOCCUS and GONOCOCCUS and non-pathogenic NEISSERIAL species?

Back 71

SUGAR FERMENTATION TESTS: (glucose, maltose, lactose & sucrose)
N. gonorrhoeae: glucose (+)
N. meningitidis: glucose & maltose (+)
non-pathogenic Neisseria: ferments all sugars except sucrose

Front 72

lipid-oligosaccharide

Back 72

LOS, endotoxic component of both N. gonorrhoeae and N. meningitidis (lacks O-side chain seen in LPS)

mediates resistance to serum bactericidal activity

Front 73

multiplication of MENINGOCOCCUS occurs where?

Back 73

outside of cells, but not once phagocytized

Front 74

what does endotoxin from MENINGOCOCCUS do?

Back 74

damages walls of small vessels

Front 75

N. meningitidis lives where?

Back 75

in NASOPHARYNX (carrier rate varies, may be ~5% in general population, but higher in homes where there has been a cause of meningococcal meningitis)

Front 76

basis of classification of MENINGOCOCCUS into serogroups:

Back 76

differences in composition of polysaccharide capsule (bacteria of groups A, B, and C are most important)

Front 77

which is encapsulated MENINGOCOCCUS or GONOCOCCUS?

Back 77

MENINGOCOCCUS

Front 78

basis for serotypes within each serogroup:

Back 78

differences bt outer membrane proteins

Front 79

appearance of virulent MENINGOCOCCUS colonies

Back 79

virulent strains are encapsulated and have SMOOTH colonise, on articifical media rough colonies (unencapsulated, relatively avirulent are often produced)

Front 80

how is MENINGOCOCCUS transmitted

Back 80

person to person (airborne respiratory droplets)
most often in crowded conditions

Front 81

MENINGOCOCCUS carrier state may last how long? what symptoms might occur?

Back 81

from days to many months, in some a mild pharyngitis and fever are all that occur

Front 82

incidence of severe disease caused by MENINGOCOCCUS:
how does it occur?

Back 82

1/50,000 per year

bacteria progress from nasopharynx to bloodstream

Front 83

incubation period of MENINGOCOCCUS

Back 83

days to a week, most serious consequence = meningitis

Front 84

MENINGOCOCCUS prediliction for what age group?

Back 84

<5 years, highest incidence in first year (but after maternal Abs are gone ~ NOT neonates)

Front 85

most common meningitis in neonates is due to:

Back 85

group B Strep or E. coli K1

Front 86

incidence of MENINGOCOCCUS increases by how much in epidemics?

Back 86

100x

Front 87

without treatment mortality from MENINGOCOCCUS meningitis is about what?
with treatment it can be less than what?

Back 87

w/o treatment ~ 85%

w/ treatment <1%

Front 88

how does MENINGOCOCCUS capsule contribute to pathogenicity?

Back 88

has antiphagocytic properties

contributes to virulence

Front 89

MENINGOCOCCUS have organotropism, what does that mean?

Back 89

localize preferentially in specific organs:
MENINGES (also skin, eyes and lungs)

Front 90

what is Waterhouse-Friderichsen syndrom?

Back 90

an uncommon occurence in MENINGOCOCCUS infection: MENINGOCOCCEMIA (may cause adrenal failure, circulatory collapse and shock with rapid death)

Front 91

If most adults have Abs that confer immunity to MENINGOCOCCUS, why do outbreaks occur?

Back 91

when diverse groups are brought together, exposure to new serotypes causes outbreaks

Front 92

Clinical picture of MENINGOCOCCUS

Back 92

clinical picture of upper Respiratory infection, high fever and signs of meningitis. Patechiae may appear followed by ecchymosis from leaky blood vessels

Front 93

Lab Dx of MENINGOCOCCUS

Back 93

blood, CSF, nasopharyngeal secretions cultured and examined for gram-neg diplococci.
can further id with:
-sugar fermentation test (4 hrs) or
-latex agglutination test (10mins) based on capsule Ag in CSF

Front 94

Treatment for MENINGOCOCCUS

Back 94

must be prompt, intravenous PENICILLIN = drug of choice
or 3rd generation cephalosporins (CEFTRIAXONE)

Front 95

Prophylaxis in household MENINGOCOCCUS contacts

Back 95

RIFAMPICIN (because effeciently secreted in saliva) or CIPROFLAXACIN (bc so potent)

Front 96

MENINGOCOCCUS Vaccines

Back 96

have been tested with moderate success
QUADRIVALENT vaccine available for groups A, C, Y, and W-135. mainly for epidemics or military

Front 97

Why does MENINGOCOCCUS Type B capsule not immunogenic?

Back 97

composed of sialic acid, not recognized by C3b complement, thus does not stimulate recruitment of phagocytes

Front 98

What does lumbar puncture determine when meningitis is indicated?

Back 98

fever in neonate (suspect group B strep or E. coli K1)
patechial rash with neuro symptoms is indicative of N. meningitidis

Front 99

How is endotoxin activity different in GONOCOCCUS (vs MENINGOCOCCUS)

Back 99

not a major factor in disease state caused by GONOCOCCUS

Front 100

GONOCOCCUS lives primarily where?

Back 100

IN GENITOURINARY TRACT

Front 101

# of serotypes of GONOCOCCUS (based on what?)

Back 101

100+ serotypes
based on antigenicity of pilus protein

Front 102

GONOCOCCUS transmission:

Back 102

STD, direct genital contact, resultin in genitourinary tract infection
-rectal and pharyngeal mucosa (non-path Neisseria also found in pharynx) and conjunctiva of newborns

Front 103

how quickly is infection by GONOCOCCUS is established?

Back 103

within an hour of exposure

Front 104

how does GONOCOCCUS invade?

Back 104

bacteria anchor to surface of epithelial cells using pili
-penetrate through surface cells and reach sub-epi CT w/in a few days
-followed by inflammation and yellow purulent urethral dicharge

Front 105

incubation period for GONOCOCCUS in
Males:
Females:

Back 105

males: symptoms appear in 2-3 days
females: most become symptomatic within 10 days (but a higher percentage of infected females remain asymptomatic)

Front 106

where might GONOCOCCUS infection spread?

Back 106

epididymis or prostate in males, to FALLOPIAN tubes in females

Front 107

what do the Pili of GONOCOCCUS do?

Back 107

associated with VIRULENCE, promote sticking to epithelial cells and impair phagocytosis by PMN leukocytes (non-piliated strains are not virulent)

Front 108

probably the 2 most prevalent communicable bacterial diseases of humans?

Back 108

gonorrhea (WW pandemic)
and infection with venereally-transmitted chlamydia trachomatis

Front 109

carrier state of gonorrhea

Back 109

common and asymptomatic (est. 1-10% of infected males are asymptomatic, even higher for females)
-can transmit infection

Front 110

complications of disseminated gonorrheal disease

Back 110

a) arthritis-dermatitis syndrome with spread to one or more joints and with skin lesions; joint infection may occur in the absence of prior overt genito-urinary symptoms
b) chronic pelvic inflammatory disease in females

Front 111

clinical picture of gonorrhea

Back 111

discharge + hx or exposure

Front 112

lab dx of gonorrhea

Back 112

-stained smears of fresh exudate (gram - diplococci within PMN leukocytes)
-culture should be done before Tx is started (oxidase +, gram - diplococci)
-dx might be difficult in chronic cases

Front 113

treatment for gonorrhea

Back 113

drug resistance = major problem

IM-Ceftriaxone and 10 day oral tetracycline or doxycycline for chlamydia (assumed present also)

single-dose Pen not recommended

Front 114

3 major forms of gonococcal resistance:

Back 114

a) Plasmid-mediated penicillinase producing N. gon (PPNG)
b) Plasmid mediated tetracycline resistant N. gon (TRNG)
c) Chromosome-mediated resistant N. con (CMRNG) {includes Pen, Tet, and some cephalosporins-- related to mutations affecting permeability; level of resistance low; treatment failure rare)

Front 115

Opthalmia neonatorum

Back 115

once ause of 50% of blindness in children

Prophylactic Tx of newborn required by law: Tetracycline or Erythromycin ointment (or dilute (1%) silver nitrate)

Front 116

Immunity against GONOCOCCUS

Back 116

can be demonstrated after infection, but weak for unknown reasons

hence, repeated attacks are common

high degree of Antigenic variation may contribute to this

Front 117

Vaccine for GONOCCOCUS

Back 117

No vaccine yet