Pasteurellaceae Lecture 20 Flashcards
Pasteurellaceae
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
haemophilus
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.
Haemophilus influenzae
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
Haemophilus influenzae physical features and things
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.
Type B strains of H flu features
dd
Pathogenesis and immunity: mucosal colonization. H. Flu
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
Pathogenesis and immunity: mucosal infections H. Flu
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
Pathogenesis and immunity: invasive disease H. Flu
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
Pathogenesis and immunity: invasive disease: H. Flu
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
Epidemiology H. Flu
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
Clinical syndromes: meningitis H.Flu
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
Clinical syndromes: meningitis 2 H.Flu
complications include seizures, cerebral edema, empyema, SIADH and herniation
mortality rate approximately 5%
long term sequelae include hearing loss, development delay, and visual impairments.
Clinical syndromes: epiglottitis H.FLu
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
Clinical syndromes: cellulitis H.FLu
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
Clinical syndromes: arthritis H. Flu
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.
Slinical syndromes: other. H. Flu
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
laboratory diagnosis H. Flu
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!!!
Laboratory diagnosis: gram stain and culture H. Flu
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.
Treatment and prevention: H. Flu
Bectalactamase production: third generation cephalosporins for serious infections. PCN and betalactamase inhibitor
conjugates PRP vaccine.
antibiotic prophylaxis for close contacts with rifampin.
Neisseriacae
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
Neisseria: physiology and structure
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-
Neisseria: physiology and structure 2
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
Neisseria: physiology structure 3
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
neisseria: physiology and structure 4
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
Pathogenesis and immunity: meningococcus
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
Pathogenesis and immunity: meningococcus 2
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
Epidemiology: Meningococcus
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
Epidemiology: meningococcus
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.
Clinical disease: Meningitis Meningococcus
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
clinical disease meningococcemia
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
clinical disease
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
Laboratory diagnosis
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
treatment and preventions
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)
Vaccines
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.
