Pasteurellaceae Lecture 20

Question 1

Pasteurellaceae

Answer 1

Haemophilis, aggregatibacter, actinobacillus, pasteurell

small gram negative rods, can be pleomorphic

facultative anaerobe

most require enriched media for isolation

of this family, haemophilus are most commonly isolated human pathogen

Question 2

haemophilus

Answer 2

relatively few species pathogenic to humans

nearly all human disease due to strains of haemophilus influenzae

colonize the upper respiratory tract in the first few months of life

other significant species: H influenzae biogroup aegyptis infeciton results in acute purulent conjuctivitis. H aphophilus and parainfluenza associated with endocarditis and infections in aimmunocomrpomised hosts.

Question 3

Haemophilus influenzae

Answer 3

Haemophilus means blood loving

indicates requirement for blood factors for growth.

Hemin or x factor:heat stable iron containing protoporphyrin essential for electron transport chain and important for aerobic growth

v factor (v for vitamin): coenzyme nicotinamide adenine dinucleotide NAD

both present in blood enriched media but must be gently heated to destroy the inhibitors of V facotr. use heated blood agar, “chocolate” agar for isolation

Question 4

Haemophilus influenzae physical features and things

Answer 4

capsulated or unencapsulated. Capsulated is typable and unencapsulated are non typable

strains without polysaccharide capsules (non-typable) cause infections of mucosal surfaces. OM, sinusitis, bronchitis, and pneumonia. Rarely diseminate

capsular polysaccharides: encapsulated strains (typable) cause majority of invasive disease. Composed of polyribitol phosophate (PRP). can express one of six polysaccharide capsules (A, B, C, D, E, or F). Haemophilus inflenza type B (HiB) accounts for 95% of all strains taht cause invasvie disease.

Question 5

Type B strains of H flu features

Answer 5

dd

Question 6

Pathogenesis and immunity: mucosal colonization. H. Flu

Answer 6

transmission from carrier to new host.

colonization must overcome nonsepcific mucociliary defenses

outer membrane proteins (OMP) p2 and p5 promote bacterial binding to mucous

LPS damages ciliated cells

adhesins and pili mediate direct adherence to nonciliated epithelial cells
IgA proteases cleave IgA

invasion into cells and subepithelial space

biding and uptake of iron and heme allow organisms to persist

Question 7

Pathogenesis and immunity: mucosal infections H. Flu

Answer 7

disease due to unencapsulated (non-typable strains)

direct movement of organisms: through nasal ostia to the sinuses

eustachian tubes to middle ear to cause otitis media

down bronchi to cause bronchitis and pneumonia

precipitating factors cigarette smoke, allergic disease, and viral infection

Question 8

Pathogenesis and immunity: invasive disease H. Flu

Answer 8

mucosa to bloodstream to distal sites

caused by typable strains (most HiB)

invade mucosa by separating apical tight junctions of columnar epithelium and moving intercellularly

bacteremia initially low in concentration but increases in matter of hours

polysaccharide capsule is antiphagocytic and major virulence factor

Question 9

Pathogenesis and immunity: invasive disease: H. Flu

Answer 9

severity of infection related to rate of clearance of bacter.ia. When bacterial Conc. > 10^4/ MI metastatic seeding occurs.

antibodies directed against the capsule stimulate phagocytosis and complement mediated activity. Antibodies formed following natural infection, vaccination, or passive maternal transfer.

risk of meningitis and epiglottitis increased in patients with no anti PRP antibodies, complement deficiency, or post splenectomy

Question 10

Epidemiology H. Flu

Answer 10

humans are only natural host

most children colonized during the first 5 years of life

person to perosn transmission through respiratory droplets

bimodal seasonal pattern with peaks Sept-Dec and march -may

children between 6-18 months at highest risk of invasive disease

prior to vaccination estimated 20,000 cases of invasive HiB anually in children <5.

worldwide HiB remains major childhood pathogen with 3 million cases and 700,000 fatalities annually

Question 11

Clinical syndromes: meningitis H.Flu

Answer 11

prior to routine vaccination was most common cause of pediatric meningitis

nonspecific signs and symptoms especially in younger children. 1-3 day history of mild upper respiratory disease. Irritability, fever, lethargy

older children may have headache, photophobia, and meningismus
fulminant disease: rapid neurological deterioration

Question 12

Clinical syndromes: meningitis 2 H.Flu

Answer 12

complications include seizures, cerebral edema, empyema, SIADH and herniation

mortality rate approximately 5%

long term sequelae include hearing loss, development delay, and visual impairments.

Question 13

Clinical syndromes: epiglottitis H.FLu

Answer 13

cellulitis and swelling of supraglottic tissues

can result in acute upper airway obstruction
peak incidence of disease in 2-4 years olds

rare in the post vaccine era

abrupt onset of high fever, sore throat, dysphagia and sepsis

airway managemnt crucial. Keep child calm. emergency nasotracheal intubation in OR (in case need of trach) by ENT or anesthesia

Question 14

Clinical syndromes: cellulitis H.FLu

Answer 14

relatively uncommon form of HiB disease

in pre vaccine era seen mostly in children <2

most located in cheek, periorbital region, or neck

manifests as fever with unilateral raised warm and tender area. may progress to violaceous hue

secondary focus may be present in 10-15% of patient

Question 15

Clinical syndromes: arthritis H. Flu

Answer 15

prevaccine leading cause of septic arthritis in children <2

most often affects single large joint

disease due to bacteremic spread

presents with fever, decreased range of motion, warmth and sweling

10-20% with contiguous osteomyelitis

requires surgical drainage and IV antibiotic therapy

can occur in older populations but usually immunocompromised.

Question 16

Slinical syndromes: other. H. Flu

Answer 16

sinusitis, otitis, and lower respiratory tract disease typically caused by non typable strains

conjuctivitis: caused by H. influenzae biogroup aegyptius

acute purulent conjuctivits

epidemics during warm months

Question 17

laboratory diagnosis H. Flu

Answer 17

high index of suspicion especially in unimmunized children

culture: blood culture shold be obtained in any child with suspected invasive disease. CSF, pleural fluid, sputum cultures may also be useful. Do not perform throat cultures in patients with suspected epiglottitis!!!

Question 18

Laboratory diagnosis: gram stain and culture H. Flu

Answer 18

Gram stain: Gram negative rods. Pleomorphic, may also appear as coccobacilli or filaments. + in 80% of patients with meningitis

culture: chocolate or levinthal agar. 1-2mm smooth opaque colonies. Statelite phenomenon.

Question 19

Treatment and prevention: H. Flu

Answer 19

Bectalactamase production: third generation cephalosporins for serious infections. PCN and betalactamase inhibitor

conjugates PRP vaccine.

antibiotic prophylaxis for close contacts with rifampin.

Question 20

Neisseriacae

Answer 20

first described by albert neisser in 1879 as that organism of gonorrhea

three genera: neisseria, eikenella, kingella

10 species of neisseria with two causing majority human disease. Neisseria meningitidis, and neisseria gonorrhoeae

nonmotile and aerobic

Question 21

Neisseria: physiology and structure

Answer 21

gram negative diplococci with flattened sides (coffee beans)

oxidize carbohydrates: can be useful i differentiating pathogenic strains

complex growth requirements and grow best on choclate agar

structures similar to other gram-

Question 22

Neisseria: physiology and structure 2

Answer 22

Polysaccharide capsule major virulence factor

basis for serotyping

thirteen serotypes of N. Meningitidis. most infections caused by a, b, C, y, and W-135

other virulence factors: pili, porin proteins, lipooligosacharide, IgA rotease, transferrin bindining protein

Question 23

Neisseria: physiology structure 3

Answer 23

pili mediate attachemnt to host cells and invasion. pili gene can be turned on and off which may aid in detachment and transmission to another host/site

proin proteins form channels for nutrients to enter cell

PorA and PorB proteins

PorB can interfere with degranulation of neutrophils

PorB facilitates invasion to epithelial cells

porB PIA antigen makes bacteria resistant to complement mediated serum killing

Question 24

neisseria: physiology and structure 4

Answer 24

LOS: composed of lipid A and core oligosaccharide. Lacks the O antigen polysaccharide of LPS. Lipid A possesses endotoxin activity. Neiseria release outer membrane blebs during rapid cell growth

transferrin binding proteins: binds uman transferrin. Allows bacteria to compete with human hosts for inron. Specificity for human transferrin likely why strict human pathogen

IgA protease: cleaves the hinge region in IgA1

Question 25

Pathogenesis and immunity: meningococcus

Answer 25

human nasopharynx only natural reservoir.

once respiratory tract colonized either develop invasive disease or develop antibody and become immune
adhere to nonciliated columnar epithelial cells in nasopharynx via pili

binding induces endocytosis into epithelial cells

penetrates epithelial barrier via phagocytic vacuoles. Able to avoid intracellular death, replicate, and migrate to subepithelial space

if antibody is insufficient and invasion occurs, individual may become bacteremic and progressively ill

bacteria in blood may seed meninges and cause meningitis

Question 26

Pathogenesis and immunity: meningococcus 2

Answer 26

antibodies against polysaccharide capsule protective

infants protected via passive transfer of maternal antibody that waned by 6 months of age

complement system important for bactericidal activity

patients with deficiences of C3, C5, C6, C7 or C8 at increased risk of infection

Question 27

Epidemiology: Meningococcus

Answer 27

endemic disease occurs worldwide.

Epidemics common developing countries.

Serotypes B, C, Y cause most disease in US and europe each causing about 1/3 of cases

A and W-135 predominate in developing countries.

meningitis belt in africa

outbreaks during pilgrimage to Mecca caused by A and W-135

Question 28

Epidemiology: meningococcus

Answer 28

humans are only natural carriers

asymptomatic carriage varies with rates <1% to 40%

carriage rates highest for school age children, young adults, lower socioeconomic status (crowding)

carriage is transient with clearance following development of protective antibodies

transmitted via respiratory droplets among people with prolonged close contact

disease most common in children <5, teenagers, yougn adults, elderly, those living in closed populations.

Question 29

Clinical disease: Meningitis Meningococcus

Answer 29

abrupt onset with HA, meningeal signs, and fever

younger children may have nonspecfic signs such as fever and vomiting

may occur with meningococcemia

mortality rate 100% untreated 10% treated

most common neurologic ocmplications: hydrocephalus, cranial nerve palsy, subdrual effeusion, cerebral edema, cerebral infarction

Question 30

clinical disease meningococcemia

Answer 30

typical presentation: short history of URI symptoms, fever, and rash

severe circulatory collapse with DIC and thrombosis of small blood vessels follows

purpura and shock can occur within hours of initial presentation

overwhelming shock and DIC may result in bilateral destruction of adrenal glands- waterhouse friderichsen syndrome

finding of petechiae or purpura in febrile child should increase index of suspicion

Question 31

clinical disease

Answer 31

primary meningococcal pneumonia: most common manifestation of disease in military recruits and 4.5% of disease in general population

Y and W-135 associated with pneumonia

other clinical syndromes include conjuctivities, pharyngitis, and arthritis

Question 32

Laboratory diagnosis

Answer 32

Microscopy: N meningitidis readly seen in CSF of patients with meningitis. Less useful if patients pre treated with antibiotics. Overdecolorized S. Pneumoniae may be confused with N. Meningitidis on gram stain

culture: gold standard for diagnosis. CSF, Blood,Petechiae. Blood culture alone is positive in 50% of patients who had received no prior antibiotics

Question 33

treatment and preventions

Answer 33

Penicillin vs ceftriaxone

betalactamase resistace: rare

penicillin binding protein mutations with intermediate sensitivity: increasing

prophylaxis to signifacnt exposure: household, child and day care, barracks CPR, intubation

rifampin, FQs, ceftriaxone, spiramycin (not sulfonamides)

Question 34

Vaccines

Answer 34

group specific capsular polysaccharides

A, C, Y, W135 (quadrivalent)

do not cover B

recommended at: 11-12 years of age, for adolescents entering college, military recruits, travel, asplenic patients or complement deficiency

two vaccines: Polysaccharide (MPSV4): unable to stimulate t cell dependent immunity to produce memory cells

conjuage( MCV4): polysacharide capsule conjugated to diptheria toxoid protein carrier. Longer lasting immunity although duration unknown preferred vaccine.