B3.014 Pulmonary Pathogens Flashcards
who is susceptible to opportunistic pneumonia?
immunocompromised patients
what types of pneumonia are typically caused by bacteria?
CAP and HAP
what are the primary bacteria that cause pneumonia?
streptococcus pneumoniae
mycoplasma pneumoniae
legionella pneumophila
what types of pneumonia are typically caused by viruses?
opportunistic (pediatric/geriatric)
what are the primary viral causes of pneumonia?
flu a and b, parainfluenza virus, respiratory syncytial virus (RSV)
what type of pneumonia are typically caused by fungi?
opportunistic (immunosuppressed, AIDS, cancer therapy, transplants)
hemolytic properties of s. pneumoniae
alpha hemolytic
what type of capsule surrounds s. pneu?
carbohydrate
>90 sertoypes
what does it mean to be naturally competent for DNA transformation?
has the ability to mutate by taking up DNA from plasmids to make itself more pathogenic
discuss the classification of streptococci
gram + chains normal flora of skin and mouth catalase negative may produce exotoxins
what types of strep are B hemolytic?
group A strep (GAS) : s. pyrogenes
group B strep (GBS) : s. agalactiae
what types of strep are alpha hemolytic?
viridans (green) strep: s. mutans
s. pneumoniae
what types of strep are gamma hemolytic?
enterococcus (GDS)
who hosts s.p.?
humans
where is asymptomatic carriage of s.p. common?
nasopharyngeal mucosa
5-75% of population
considered a commensal
how does transmission of s.p.?
respiratory droplets
how do most cases of s.p. arise?
spread of endogenous organisms
our own natural flora gets into the wrong niches
other than pneumonia, what common illnesses develop as a result of s.p.?
sinusitis, otitis media, meningitis
what are predisposing factors for getting s.p?
respiratory viral infections
what is pneumonia?
aspiration of bacteria and replication in alveolar spaces
how long is the incubation period of pneumonia?
1-30 days
what are symptoms of pneumonia?
abrupt onset of fever and shaking chills
pleurisy, productive cough, blood tinged sputum
risk factors for pneumonia
antecedent viral infection of resp tract, especially influenza
smoking
age <2 or >65
hematological disorders, asplenia, chronic pulmonary disease, diabetes, renal
how can you differentiate typical vs atypical pneumonia?
based on symptoms atypical "walking" pneumonia: -slow onset -moderate fever -non-productive cough -headache
key atypical pneumonia pathogens
chlamydia pneumoniae legionella pneumonia mycoplasma pneumonia chlamydia psittaci coxiella burnetii some viruses
describe meningitis
100% mortality without antibiotic treatment
25% with treatment
inflammation frequently leads to permanent brain damage, blindness, hearing loss, learning disabilities
describe otitis media and sinusitis caused by s.p.
50% of middle ear infections
sinusitis occurs in all age groups
can develop into megingitis
virulence factors of s.p.
polysaccharide capsule
C polysaccharide
describe the s.p. polysaccharide capsule
90 serotypes
essential for pathogenesis
anti phagocyctic
immunogenic
describe the s.p. C polysaccharide
complex of phosphorylcholine, peptidoglycan and teichoic acid
common to all serotypes
present in urine and serum during infection
what toxins are associated with s.p.
pneumolysin
autolysin
IgA protease
describe pneumolysin
cholesterol dependent pore forming toxin
toxic to bronchial epithelial cells
activates classical complement pathway
describe autolysin
binds to cell wall
degrades peptidoglycan, resulting in bacterial cell lysis
releases pneumolysin from cell
releases cell wall components that activate the inflamm response
antibodies to autolysin can be protective
describe IgA protease
blunts mucosal adaptive immune response
what are other characteristics of s.p. culture other than hemolysis/shape/catalase neg
bile solube
optochin-sensitive
Quellung (swelling) reaction: shows capsule on bacteria
where can C polysaccharide be found?
urine and serum
how is capsular antigen detected?
latex agglutination assap
what MIC values are considered susceptible?
<2 ug/ml
what MIC values are considered resistant?
> 8 ug/ml
DOC for pneumonia
penicillin (for sensitive isolates); vancomycin or fluoroquinolone + 3rd gen cephalosporin
PPSV23 (Pneumovax)
pneumococcal polysaccharide vaccine
covers most bacteremic strains (23)
capsular type-specific antibody is protective
recommended for: adults >65, chronically ill, and immunocompromised kids >2 years
PCV7 (Prevnar)
pneumococcal conjugate vaccine
capsular antigens from 7 serotypes conjugated to a mutated diphtheria toxin
immunogenic in children and infants
recommended for all children <2 and at risk <6
PCV13 (prevnar13)
capsular antigens from 13 serotypes conjugated to a mutated diphtheria toxin
children 6-17
adults >50
describe the classification of legionella pneumophila
gram negative bacillus
does not stain well
motile, catalase positive
fastidious
what does l. p. require to grow?
L-cysteine
ferric ions
pH 6.9
how is l.p. transmitted?
environmental pathogen no person to person transmission found in water and soil intracellular symbionts of amoebae inhalation of aerosols containing infection organisms
common sources of l.p
air conditioning cooling towers medical respiratory equip showers whirlpools humidifiers
when are legionella outbreaks most common
late summer-fall
risk factors for legionella
advanced age smoking heavy alcohol use transplant recipients immunocompromised (diGeorge)
what is l.p.’s mechanism of action
infect alveolar macrophages
-MOMP (major outer membrane protein): binds C3 and facilitates entry into macrophages
bacterial replication in phagosomes using T4SS effectors to block acidification/fusion with lysosomes
-“replicative vacuoles” surrounded by ER
virulence factors of l.p.
hemolysin: tissue degradation, lysis of RBCs
phospholipases: vacuolar escape, surfactant degradation
incubation period of l.p.
2 to 14 days
symptoms of l.p.
moderate fever headache slight or non-productive cough fatigue anorexia GI symptoms hyponatremia
l.p mortality rate
15-20%
sporadic disease that is frequently misdiagnosed
main difference between Pontiac fever and legionella pneumonia
Pontiac fever 0% fatality
higher attack rate but hospitalization uncommon
gold standard for l.p. identification
culture: growth on buffered charcoal year extract (BCYE) agar only
legionella urine antigen: detects only serotype 1 L. pneumophila (majority of infections)
antibiotics that achieve high intracellular concentration against l.p.
IV fluoroquinolones
IV azithromycin
how to prevent legionella
identification of source increase water temp hyperchlorination removal or scale from water tanks routine monitoring
describe the features of mycoplasma
smallest free living organisms slow growth (1-6 hours) lack cell walls: -cell membranes contain sterols -pleomorphic (different shapes)
what diseases results from mycoplasma pneumoniae?
atypical pneumonia
tracheobronchitis
mild upper respiratory infections
joint infections
m. p. cell shape
intracellular network of protein filaments cytadhesin organelle (arrow): membrane bound cylindrical extension at one pole that penetrates membrane and binds respiratory epithelial cells
spread of m.p
respiratory secretions
incubation time of m.p.
1-3 weeks
when are infection rates of m.p. highest?
crowded conditions
frats, dorms, schools
older children, adolescents, young adults and HIV patients most susceptible
pathogenesis of teacheobronchitis and pneumonia
- binding of ciliated respiratory epithelial cells
- production of phospholipases and peroxides
- ciliostasis, leakage of epithelial cells
- infection of lower resp tract
- IL-1, TNF a
- influx of PMNs, T and B cells
m.p. symptoms
headache fever pharyngitis dry, nonproductive cough no elevation of WBCs bilateral, diffuse infiltrates skin rash
how long does m/p/ last
4-6 weeks
m. p. culture characteristics
medium must contain serum or cholesterol
colony formation in 206 weeks
mulberry/fried egg like colonies
m. p. serological tests
cold agglutinin assay
complement fixation assay
ELISA for IgM/IgG
PCR- gold standard
what antibiotics are mycoplasma resistant to?
penicillins
cephalosporins
glycopeptide antibiotics
-all cell wall inhibitors
drugs of choice for m.p.
tetracyclines
macrolides
fluoroquinolone
what causes influenza
influenza virus
what causes croup
parainfluenza virus
what causes bronchiolitis
RSV
what causes bronchopneumonia
influenza virus, RSV, adenoviruses
main virulence factors of influenza
Hemagglutinin -18 subtypes -sialic acid receptor Neuraminidase -11 subtypes -sialidase M2 ion channel -sense acidification in the endosome M1 protein -structural NP NS1 -reprograms host cell to replicate ssRNA
symptoms of the flu
acute febrile self limited headache malaise myalgias nasal obstruction discharge sore through cough
flu attack rate
10-40%
when is the flu virus stable
low humidity and cool temps
what is desquamation of mucus secreting and ciliated cells
cilia and mucous are disintegrated resulting in a loss of defense against respiratory infections
likely a cause of secondary infections
mediators of flu cytokine storm
IL-6 -fever, acute phase response -secreted by macrophages TNF-a -causes fever and cachexia IFN a/b IL-1 -produced by macrophages -proinflamm and fever inducing IFN-y -innate and adaptive immunity -produced by lymphocytes
what cytokines induce the antiviral state
IFN a/b
what type of genetic mutation results in antigenic drift
point mutations in H and N
what type of genetic mutation results in antigenic shift
major change in H (sometimes N)
genetic reassortment
what family do RSV, hMPV, and parainfluenza virus belong to?
paramyxoviruses
describe paramyxoviruses
enveloped
pleomorphic virions
contain non-segmented negative ssRNA
induce syncytia (multinucleated cells)
general paramyxoviridae structure
attachment proteins differ between viruses -parainfluenza/mumps: HN protein -measles- H glycoprotein -RSV- G glycoprotein all have F (fusion) protein
where does DNA replication occur for paramyxoviridae?
outside of the nucleus
when do RSV epidemics occur?
winter
who is at risk of RSV?
1 cause of bronchiolitis and pneumonia in children <1 in the US
-congenital heart disease, bronchopulm dysplasia, immunodeficiency
significant cause of resp disease in older adults
-stem cell transplants, severe heart disease, COPD
RSV symptoms
fever
chills
cough, congestion, coryza, rhinorrhea, conjunctivitis
bronchiolitis- wheezing, shortness of breath
pneumonia
apnea spells in infants
RSV diagnosis
rapid antigen detection from aspirates
RT-PCR from bronchial washes
culture difficult and too slow
RSV treatment
supportive care -fluids and resp support aerosolized ribavirin -severely immunocompromised humanized monoclonal anitbodies -protect at risk infants no vaccine
describe hMPV
human metapneumovirus
causes 5-20% of pediatric URIs and LRTIs (serology)
-90% of people have it by 5, 100% by adulthood
clinical symptoms indistinguishable from RSV
supportive treatment
parainfluenza virus features
5 serotypes
reinfection common
negative ssRNA enveloped virus
pathogenesis of parainfluenza
cause illness in the large airways of the lower resp tract
- tropism for ciliated epithelial cells
- croup, bronchiolitis, also pneumonia
immune response to parainfluenza
humoral -neutralizing antibody to surface proteins -mucosal IgA can help prevent infection cellular -cytotoxic T cells
who is susceptible to parainfluenza
severe disease in adults and peds w hematopoietic stem cell or solid organ transplants
