Ch 22: Respiratory System Infections Flashcards
Above the epiglottis
upper respiratory tract
most upper RTI are relatively mild
below the epiglottis
lower respiratory tract
lncludes the bronchi, bronchioles, and the alveoli
lower RTI are usually more severe, as they effect gas transfer
look at figures
22.3 and 22.2 pg 960 and 961
Normal microbiota of the respiratory system
some (but not all) organs and surfaces of the body are normally colonized by bacteria
called the resident microflora or commensals
the upper RT is heavly colonized while the lower RT is generally sterile or has a very low number of transient bacteria
microbiota of the nose
bacteria flora found just inside the nose resembles the skin
CNS (coagulase negative staphylococci)
virdians streptococci
staphylococcus aureus
coryneforms
neisseria spp
haemophilus spp
Staphylococcus in the nose
normal microbiota of the RT
colonizes the anterior nares primarily but also some in the phaynx (nose picking region)
coagulas positive
a major and serious pathogen of the skin, soft tissue, RT and other parts of the body
found in about 30% of the population
coryniforms
gram +, aerobic, rod and pleiotrophic shaped
dessication resistant
Neisseria and haemophilus
fragile gram -ves, = gram + antibiotics work agaisnt them
are strep penicillin resitant
nope
what do we use in North america instead of methicillin
oxicillin
Different types of carriers of nasal staphylococci
persistnet carriers (20%) that carry a specific strain
non-carriers (20%) that almost never carry SA
intermittent carriers (60%) acquire and lose different strains of staph. aureus
SA tends to be disseminated from nares to other body parth and other people
nasal viridians streptococci
alpha haemolytic streptococci other than strep. pneumoniae
strep. salivarius, milleri, gordonii
Nasal neisseria spp
gram negative cocci, often in pairs
catalase and oxidase positive
microaerophillic, grow best in higher CO2 conc.
Nasal Haemophilus spp
non-motile, gram negative rods
fastidious
grow best in elevated CO2 conc
capsulated
Nasopharyx
aerobic region with high bacterial population
mucus covered epithelial cells
therefore, bacterial colonizationis either inteh mucus or to underlying cells
most epithelial cells have about 10-50 cells attached to them (quite a small amount)= sparse colonization
co2 incubate
5% co2 rich atmosphere
dats a lot
normal microbiota of the nasopharynx
staph aureus (20% of pop)
a-haemolytic strep, gamma-haemolytic strep
strep pneumonaie (6%)
neisseria spp
=> N. meningitidis, N. subflava, N. sicca
Haemophilus spp.
=> H. influenzae, H. parainfluenzae
Obligate anaerobic gram negatives of the nasopharynx
fusobacterium
preotella
prophyromonas
biofilms on teeth
and inflammation of the gums
=> these implies that these bacteria could enter the bloodstream through the capillaries in the gums
Obligately anaerobic gram positives int eh nasopharynx
peptostreptococcus
mouth full of air does have strict anerobe living in anerobic pockets and sub-structures
Moracella catarrhalis in the nasopharynx
aerobic, gram-negative cocci usually in pairs
catalse positive, oxidase positive
children generally colonized, frequent cause of sinusitis and otitis media, not common in adults
The mouth, a complex enviroment for bacteria
hard surfaces, 20% of the area of the mouth is the surface of the teeth
keratinized mucosa= skin
non-keratinized mucosa
regions which can become anaerobic
gingivial crevice
saliva
neutral pH
contains proteins, glycoproteins, mucins, carbs, organic nitrogen compounds
basically, non-extreme environment provides a good growing area for many bacteria
What must resident bacteria of the mouth do
attach to solid support or reproduce faster than alive removal rate
epithelial cells subject to desquamation
teeth subject to mechanical forces
protected areas around teeth and tongue
formation of biofilms on hard surfaces
over 200 species of bacteria have been isolated from teh mouth, over 500 other species have been detected by moleuclar techniques
Oral streptococci
gram positive, aerotolerant, fermentative in diploids or chains
streptococci in general =>divided into 4 major groups
mitis group, found mostly in the dental plaque including strep mitis, sanguis, parasanguis
mutand group, also in plaque, strep mutans, sobrinus
salivarius group, found mainly on mucosal membranes
angiosus group, strep anginosus, intermedius
Actinomyces of the mouth
non-motile, non-spore-forming, gram + pleomorphic (bumpy and lumpy even y shaped) or branching rods
facultatively anaerobic, ferment sugars to acid
opportunisitc pathogens and associated with dental caries
=>dental biofilms
=> ferment acid in biofilms, phosphate is mobalized out of the bones of teeth (mineralization) = cavities
antimyces naeslundii
=> nasty pathogen, opportunistic
=> cavities that can cause absesses that may end up degrading the jaw bone
Veillonella spp of the mouth
anaerobic gram negative cocci arranged in pair, chains and clumps
co-aggrefate with other oral bacteria to initiate biofillm formation
Fusobacterium of the mouth
fusiform morpology = cigar shaped, with tapered ends
bridging species, attach to first colonizers of teeth then to late colonizers
Porphyromonas
proteolytic, ferment aa = > stricland ferementation (one aa ox another is red)
second biofilm colonizer of teeth (fusobacterium is the first)
por. gingivalis is major cause of periodontitis
por. endodontalis can degrade bone, cause endodontic infections
Streptococcal infections (strep throat)
streptococcal pharyngitis caused by streptococcus pyogenes
group A strep (GAS) by the lancefield system
symptoms include fever, pharynbgeal pain, inflammation and erythema, swollen tonsils with pus, petechiae
transmission by direct contact or airborne (droplets)
scarlet fever
strep throat
GAS
similar to pharyngitis with a diffuse bright red rash
rash due to the production of erythrogenic toxins by GAS
Treatment of strep thoat
Treatment - antibiotics - beta lactams like amoxicillin or a cephalosporin such as cefadroxil
if patient is allergic to or isolate is resistant to beta lactams then clindamycin, azithromycin or clarithromycin is used
Bad things that can happen after a sore throat
common with strep infections
=> sequelae of strep infections
Rheumatic fever
acute glomerulonephritis
sydenhams chorea
Rheumatic fever
an auto-immune disease where the immune system attacks heat tissue after a GAS infection
major reason why we use antiobiotics for GAS infections
fever, joint pains, polyarthritis which is migratory and involves multiple joints, abdominal and chest pain, erythema marginatum, nose bleeds and vomiting
Carditis, other damage to the mitral valve
heat murmurs, heart enlargement, congestive heart failure, cardiac arrect and death
2-3 months after GAS infection
Acute glomerulonephritis
inflammation of renal glomerulus with lesions
hematuria (blood in urine) and proteinuria (abnormally high levels or protein in urine)
Sydenhams chorea
muscle spasms, weakness, awkwardness and tendency to drop things
other sequelae that GAS can occur
wide range of different diseases in different organs
impetigo
puerperal sepsis (childbed fever)
toxic shock syndrome (toxins produced by bacteria [with strep] toxin diffuses across a mucus membrane, and is dissiminated throughout the circulatory system)
pneumonia (mostly strep pneumonia, but can be caused by other species like GAS, staph, gram neg, and atypical pneumoniae)
bacteria, septicaemia
septic arthritis, osteomylitis (bone infection)
endocarditis, pericarditis
bacterimia
the presence of bacteria in the blood stream
septicaemia
the presence of and reproduction of bacteria in the blood stream
GAS virulence factor
SpeB
streptococcal pyrogenic extoxin B
SpeB can degrade Ab into small fragments therefore, no neutralization or opsinization
complement protein C3b degraded therefore no opsinization
GAS virulence factor
SpeA
streptococcal pyrogenic exotocin A, erythrogenic toxin
found on a temperate phage of GAS, phage integrates into GAS, and the toxin is integrated.
attacks capillary endothelial cells and causes them to dialate (erythrogenic toxin)
Also the cause of streptococcal toxic shock syndrome (STSS)
GAS virulence factor
SpeA and STSS
simultaneously bind to MHCII moleucles and TcR
=> superantigen, activates T cell even if not cognate.
leads to the activation of a large number of T cells
increased secretion of cytokine such as TNFa, interlukin 1 and interferon g
activates the complement (complement doens’t work great against these floating toxins, attack your own cells), coagulation (clots to hide from immune cells, and dissemination from the body) and fibrolytic cascades resulting in hypotension and multiorgan failure
GAS virulence factors
The M proteins
probaby the most important virulence factor of the GAS
M protein is covalently attached to the peptidoglycan layer
antigenic - 83 serotypes
prevents complement activation and binding
can activate platelets for coagulation
redundancy in virulence factors
implicated in rheumatic heart disease
=> antibodies to M protiens are often cross reactive to cardiac tissue, big MAC attack of the heart
why does strep cause so many diseases
has a lot of virulence factors
How does the M protein works to cause virulence
binds kinigen and drabykinin is released with leads to inflammation
binds plasminogen which breaks down frigrinogen in local blood clots
M proteins interact receptor on monocytes resulting in production of inflammatory cytokines
Capsule in GAS
virulence factor
GAS capsule is composed of hyaluronic acid, a polymer of alternating N-acetylglucosamine and glucuronic acid
=> similar to stuff seen in body, poorly immunogenic and seen as self
poor immunogen, Abs to GAS hyaluronic acid not detected in humans
in mutant GAS which lose the ability to produce capsules resistance to phagocytic killing and mouse virulence decreased 100-fold
GAS virulence factors
streptolysin O
oxygen labile, pore-forming cytolysin
causes lysis => why it is called a lysin
toxic to a variety of cells including neutrophils
GAS virulence factors
Streptolysin S
produced by streptococci grwoing int he presence of serum
by weight one of the most potent cytotocins known
GAS virulence factors
DNase
serve to liquify pus and facilitate the spreading of streptococci through tissue
also release from neutrophil DNA nets in capillaries
GAS virulence factors
Hyaluronidase
degrades hyaluronic acid present in connective tissue
GAS virulence factors
streptokinase
dissolution of clots by catalysing the conversion of plasminogen to plasmin
GAS virulence factors
C5a peptidase
specifically cleaves the complement protein C5a
GAS virulence factors
Streptococcal inhibitor of complement (Sic)
inhibits lysis by MAC
STATS on GAS virulence
responsible for over 500 000 deaths each year
600 milliion new cases eaach year of S. pyogenes pharyngitis
30 million cases of rheuamatic fever every year
Cause of diphtheria
Corynebacterium diphtheriae
gram +, club-shaped bacterium
airborne transmission
colonization of the nasopharynx
production of an A-B toxin which binds to human EF-2 and inhibits protein translation = cell death
-> each toxin, inhibits many many elongation factors
=> toxin human lethal does estimated <0.1ug/kg
the gene encoding the toxin (dtx) is actually carried on a bacteriophage
=> strains are lysogenized with the phage
Other causes of Diptheria
Corynebacterium diphtheria (main)
occasionally C. ulceranc, C. pseudotuberculosis
C. ulcerans, and diptheriae can also cause skin leasions and infections
Symptoms of Diptheria
sore throat, low fever
formation of the pseudomembrane in the back of the throat
=> thick, grey membrane made up of dead cells, red blood cells, bacteria and fibrin
=> can expand to the nasal cavity and obstruct the pharynx or trachea leading to suffocation
toxin is absorbed into the bloodstream and ciculated causing heart damage and verve damage
irregular heartbeat, cardiac dilation from muscle weakening and thinning, shorness of breath
nerve damage leads to weakness, paralysis of tissue in the RT, eye, or total paralysis
Case fatality rate of diphtheria
5-10% with higher death reats up to 20% amoung persons younger than 5 and older than 40yrs
Treatment of diphtheria
b-lactam antibiotics such as amoxicillin, penicillin, or erythromycin
antiserum or antitoxin can be administered to prevent damage due to the toxin
=> emil adolph con bohring and shibasaburo kitasato developed an antitoxin based on immunization of horses in 1891
The history of diphtheria
see slide idk im lazy
dog sledding
Chapter 22 lecture 4
Diphtheria prevention
inactivated toxin (toxoid) vaccine
- DTaP
- DTaP-IPV-HPV (diphtheria, tetnaus, acellular pertussis, polio and haemophilus influenza type B) at 2, 4, 6 and 18 moths
-Tdap-IPV at school entry and Tdap at 15yrs
Prevalence of Diphtheria
in Canada, prevalence was about 80-100/100 000 in the 1920’s
in 1936, it was 20 in the 1964 pretty much 0
usually less that 100 cases per year, now about 0q
Bacteria pneumonia
pneumonia is inflammation in the lungs and fluid accumulation in the alveoli
pneumonia can be causes by bacteria viruses, fungi, or by non-biological events
most pneumonia is caussed by bacteria and most bacterial pneumonia is caused by streptococcu pneumoniae
the single largest infection cause of death in children worldwide
=> killed 800 000 under the age of 5 in 2017
=> 15% of all deaths of children are under 5 yrs old
Bacterial pneumonia in Canada
Together with influenza, pneumonia was the 7th leading cause of death in Canada in 2019
6893 deaths
20/100 000 / year in Canada
24 761 cases of community- aquired pneumonia in Canada that required hospitalization
Pneumonococcal pneumonia
Streptococcus pneumoniae
humans are the only reservoir
droplet transmission, colonization of upper RT followed by aspiration into lungs
Symptoms of pneumococcal pneumonia
abrupt onset
fever, chils
difficulty breathing
productive cough
rust coloured sputum
What other diseases are pneumococcal pneumonia present as a co-infection in// opportunitic infection
influenza
chronic lung disease
smoking
aspiration due to intoxication
Case-fatality rate of pneumococcal pneumonia
20-40% in hospitilized cases (in the past)
2-10% with antibiotics
20-40% with underlying disease
Treatment of pneumococcal pneumonia
amoxicillin
azithromycin, clarithromycin
Cefpodoximie, cefuroxime
Doxycycline
Fluroquinolone such as levofloxacin, moxifloxacin or gemifloxixcin
penicillin G
prevention of pneumococcal pneumonia
2 vaccines Pneumovax23 and Prevnar13
pneumovax23 protects against 23 different serotypes and prevnar protects against 13 serotypes
protects agaisnt the capsule of the bacteria
List of different bacteria that cause atypical pneumonia
Haemophilus influenzae H. influenzae A HiB Mycoplamsa pneumoniae Klebsiella pneumoniae Neisseria menigtidis Staphylococcus aureus Psuedomonas aeruginosa chlamydia
Atypical pneumoniae and Haemophilis influenza
small gram - coccobacilli, facultatively anaerobicx, fastidious
=> chocolate agar
nonencapsulated strains (non-typeable, NTHi) and HiB
commensals but also spreaad by aerosols
similar symptoms to pneumococcal pneumonia
Atypical pneumoniae and Mycoplasma pneumoniae
small cell wall-less (no affected by beta lactams= selection method) organisms
actually gram + , small genome (<1 Mbp)
0.1-0.2 um diameter, 1 um length
usually mild and self-limiting disease
low fever, persistent non-productive cough
also pharyngitis, earache, headache, malaise
hard to isolate on agar, may require 30days incubation
airborne
damage to diliated epitheliad cells by tip organelles (from twictching motility) and H2O2 production leaads to an inhibtion of ciliary action, expultion of mucus inhibited
PCR, serological test is also used
treamtent with azithromycin or clarithromycin, doxycycline, fluoroquinolones
Atypical pneumoniae
Chlamydial pneumoniae
parrot fever
cause by chlamydophia pneumoniae, psittica, trachomatis
obligate intracellular parasites, gram -
incubation period of 3-4 weeks
abrupt onset, headache, fever, myalgia, nausea and vomiting, cough all lasting 3-4 weeks
treatment: C. pneumoniae = azithromycin ort tetraculine
C. psittaci = tetracycline
Klebsiella pneumoniae
atypical pnuemonia
gram negative, encapsulated, fermentative, facultatively anaerobic bacilus (releated to e.coli as it is in the enterobacteria)
humans are primary reservoir, about 3% carry K pneumoniae in their nasopharynx
fever, chest pain, cough with current jelly sputum
30-50% mortality, up to 100% with underlying complications
Atypical pneumoniae
klebsiella pneumoniae treatment
treamtent with 3rd/ 4th generation cephalosporin, fluroquinolones, carbapenam if HAP
major problem with extened spectrum beta lactamase (ESBL) or carbapenam-resistant enterobacteria (CRE) or (KPC) strains
Atypical pneumoniae
Pseudomonas aeruginosa
Gram negative, aerobic, non-spore forming, non fermentative bacillus
causes pneumonaia associated with cystic fibrosis and ventilator use in hospitals (VAP)
20% of all cases of VAP,m 15% mortality rate
Treatment of pseudomonas aeruginosa atypical pnuemoniae
carbapenems (meropenem), cephalosporins (ceftaxidime, cefepime), aminoglycosides (gentamicin, tobramycin, and amikacin) and fluroquinolones (ciprofloxacin and levofloxacin)
Atypical pneumonia
staphylococcus aurues
gram positive cocci found in clusters, catalase positive, oxidase negative, facultatively anaerobic, fermentative
produces bright yellow or golden coonies
20-30% of hospital-aquired pneumonias
typical bacterial symptoms except for nectrotizing pneumonia
(fever, rapid onset, chills, cough non-productive or productive (blood or not,m and apperance of the blood))
Staph aurues atypical pneumonia symptoms
abrupt onset of fever, chest pain and a productive cough with purulent sputum, which can be blood-tinged
some S.aureus strains carry the panton-valentine leukocidin (PVL)
Kills macrophage and causes tissue necrosis and hemorrhaging.
See slides for 2019 Tuberculosis stats
winnipeg manitoba
Mycobacteirum tuberculosis is the most common human TB pathogen.
what are the others
Once was the most common human pathogen, now, might be heliobactor pylori (1/3) (1/4) people are infected by MTB
other species
mycobacterium africanum, M. micoti, bovis also cause human disease
Mycobactireum avium/ intracellulare complex causes TB in immunocompresised himans
Mucpbacterium Kansasii, fortunitum, canetti can cause TB or non-TB mycobacterial infections
Mycobacterium tuberculosis
gram positive although not readily stainable by the gram strian
=> now use an acid fast stain for MTB
bacilli, 0.3 - 0.6um diameter, 1-4 um long
cells grow in serpentine, parallel bundles
aerobic (best growth with 5% CO2) but tolerates almost anaerobic conditions if adapted slowly
optimum growth temperature 37C, pH 6.5-7
considered to be a slow grower mycobacterium
Lowebsteub-Jensen agar
for MTB
early methods to isolated MTB from agar media were not successful
better results were obtained by heating protein (from whole eggs) to solidify it in a solution containing potato flour, glycerol and salts
malachite green was added to make the medium selective by inhibiting sputum contaminants
still requires 18-24 days to detect micro-0colonies and 6-8 weeks for full growth of colonies
Middlebrook Media
synthetic media developed in the 50’s
for MTB
defined salts, vitamins, oleic acid, albumin, catalase, glycerol, malachite green
7H10 contains glu
7H11 contains casein hydrolysate
both are solid media containing agar
7H9 is a similar compositionliquid medium
reduces the time to observe micro-colonies to 10 days
BACTEC 460
MTB specimens are added to a 20mL glass bottle containing 7H9 broth plus BAS, catalase, antibiotics and 14C labelled palmitic acid
mycobacteria oxidize teh labelled palmitic acid to 4CO2
the headspace of the bottles is smapled and the gas passess to a scintillation counter
9-14 days for detection of growth
Signs and symptoms of TB
can be a difficult diagnosis especially for non-pulmonary forms
productive cough for more than 3 weeks (streaked with blood) like Klebsellia (chunks) and then to full streaks from haemoraghing
fever (night sweats)
anorexia and weight loss
malaise
chest pain
Lab test for TB AF
acid fast strain
70% sensitive
Incidence rate and TB
most diseases have a U shaped curve,TB has the opposite. The incidence rate rises with increasing age, drops a little bit (cause they die), then spikes again
not very high in youger childern >5/10 like most infectious diseases
Lab test fort TB
chest radiography
usually one or both upper lobes
consolidation, infiltration, cavitation and calcified nodules may be visible
not very sensitive, nodules need to be fairly large to detect
Lab test for TB skin test = Mantoux
an injection of purified protein derivative (PPD) from a culture of mtb inhected under the skin
induration of greter than 10mm indicates at least exposure to mtb
Tuberculosis Transmission
an airborne infection
=> dropletes of 2-4um can penetrate to the alveoli
=> droplets produced by infected person coughing and sneezing especially when they have active TB and a cavitation
=> mtb is a fairly resistant to desiccation
TB can also be transmitted though milk and food
=>pasteurization of milk and use of pasteurized milk in cheese-making, etc. has largely eliminated this route
Trasmission rates of TB
only about 5-10% of newly infected people go on to develop TB immediately those who are latent have houts a 10% lifetime risk of developing TB
reactivation of latent TB as immunity waves
Dissemination of TB
droplet to phagosome
mtb is taken into the lungs as a < 5mm droplet or droplet nuclei
penetrates to the alveoli
taken up by an alveolar macrophage or a lung DC by pasive phagocytosis
=> can reproduce in the macrophage but not DC
after phagocytosis, most bacteria should be killed but mtb survies and replicates inside the macrophage
Dissemination of TB
Inside the infected macrophage
eventually the macrophage is killed, bacteria become extra-cellular and infect more macrophage.
mtb can also infect epithelium and other cell types
The infected macrophage returns from the alveoli to lung tissue, migrates to local lymph node
=> a local inflammation takes place
=> more macrophage are recuited to the site of infection
=> they surround the infected macrophage in ayers with tighly apposed membrane which interdigitate
=> macrophage becomes epitheliod cells
this is called a granuloma
Dissemination of TB
Granuloma maturation
over time the individual macrophages fuse to become giant cells with multiple nuclei
macrophage inthe centre of the granuloma die and new macrophage are recuited to the periphery
granuloma exapmds
T cells become activated and home to the granuloma
granuloma now consists of a core of macrophage/ giant cells with live mtb and a periphery of T cells and fibroblasts
Dissemination of TB
cytokines
activated T cells secrete IFNg and TNF
=> macrophage become activated adn more successful at killing mtb
fibroblasts secrete collagen and other material to form a fibrous shell to the granuloma
calcium may be deposited around the granuloma to seal it off
90% of infected people this is the end of the story
over time the mtb die off the and granulonas become sterile
Dissemination of TB
the 5-10%
these ppl develop primary tuberculosis
also reactivation of latent TB with age or stress
mtb survives somewhere in the obdy
previously contained granulomas can enlarge
cells in the centre of the granuloma die, lyse and produce a ssheesy substance= caseous granulomas
granulomas expant by recruiting or reproduction of cells at the periphery and increasing necrotic core
Dissemination of TB, errosion of the granuloma
may erode into a blood vessel and MTB spreads through the circulatory system
may erode into an alveoli and spill out caseous material
pulmonary cavitation
plenyy of oxygen in the cavity higher rate of replication of mtb
=> high numbers of cells in the cavity 10^10 cells
caseous material is very irritating
=coughing, sneezing and is highly infectious
MTB treatment
streptomycin was the first antibiotic found to have any effect on mtb. (first random control done). 5 years later, the TB emerged with resistance. Before this you were sent to an sanitorium = you go into remission by relieving stress or ya die
Eventually pateitns developed streptomycin-resistant mtb
this lead to the idea of multiple antibiotic therapy
only when 3 different antibiotics were used simultaneously did patients recover were used simultaneously did the patient recover without re-emergence
2 years with SM alone
12 moths with combination therapy
DOTS therapy
for mtb
directly observed treatment- short course
the current WHO recommended treatment
4 drugs for 8 weeks
= isoniazid, pyrazinamide, rifampicin, ethambutol
followed by 2 drugs for 18 weeks
= isonizid and rifampicin
second line antibiotics for mtb
amikacin or kanamycin
capreomycin
cycloserine
ethinoamide
moxifloxacin or levofloxacin
new anti-TB antibiotics
BPaL regime
bedaquiline
pretomanid
linezolid
clofazimine
Bortadella Pertussis
whooping cough
=> peridoxal coughing, non-productive then the big inhale
Gram-negative cocco-bacillus. Doesn’t stain very well
aerobic, oxidase postive
motile, encapulated and humans are the only reservoir
7-10 day incubation
colonization of bronchi and trachea
=> different from pneumoniae and tuberculosis which colonize the alveoli
Filamentous heamaglutin
causes rbc to agglutinate, on the surface of bacteria like pertusis (which has two types)
fimbriae
10-12 nm in diameter
involved in specific adhesion
virulence factors for UTI e.coli infections
bind bacteria and mediate specific ahesion to certain cell types
protractin
adhesion moleucle?
pertussis toxin
A-B type toxin
one subunit binds, the other goes into the cell
exotoxin
causes cell death, and medation of inflammation
Pertusis tracheal toxin
Prevents cillary motion
=> no mucus expultion in the trachea
pertusis adenylate cyclase
targets immune cells
kill wbc
Pertussis cataral stage
one of three stages of disease progression
moderate symptoms
runny nose, coughing sneezing, low fever
still highly infective during this stage for pertussis = before symptoms
Pertussis paramoxamal stage
whooping sounds
can break your own ribs coughing, or brain damage
final pertussis stage
convalence
declinign cough
100 day cough
pertussis complicaitons
pneumonia
encephalopacy
pertussis vacination
1930s heat killed, whole cell, inactivated vaccine
=> high effacacy, life long immunization
however later on, two infants died after vaccination
led to the acellular pertussis vaccine
=> aP, ap acellular pertussis
. against pertussis toxin, filamentous haemaglutin, and later, protectin and type 2/3 fibrian
=> processed to remove LPS
need a whole cell booster shot for the acellular vacccine
legionares disease
relativly new, non-cultivatable
media has charcoal and cysteine
limited human to human tramsmission
grow better in macrophages than on a petri dish
Influenza
ingle-stranded negative sense segmented RNA envaloped virus (8segments), 8 different genes
=> may lead to re-assortemented viruses
viral envelope contains 2 virus encoded protiens
h or hemagglutin
N or neuraminidase
4 species A, B, C, D
aerosol, direct and indirect contact transmission
+ sense
protein synthesis
- sense
needs to be converted to + to make protein
=> replication intermediate is these doubled stranded intermediate to convert the two strands
human glycolylation of protiens
siallic acid
=> leads to tethering of viruses from budding
neurimidase protein is important to cleave this
heamaglutaninn
binds to siallic acid receptors on epitheial cells
sticky part of virus
trophisms?
virus is taken into epithelial cell
acidifies vesicle, then the heamagluttin changes in shape to mediate the fusion of the lysosome with the viral membrane, pops into the cytoplasm of cell
Viral M proteins??
???
figure 22.17
memorize
signs and symptoms of flu
abbrupt onset
quick fever, then done
multiple hot cold hot cold events (fever, then chills)
non-productive cough (will NEVER cough up blood0
time of season is important
Animal reservoirs of influenza A
Gulls, terns and shorebirds or waterfowl (ducks, geese and swans)
18 known H subtypes and 11 N in birds
almost every combination fo H and N occur
Pigs
=> though that flu is a zoonotic disease from birds maybe via pigs or other animals
Epidemics and Pandemic with Influenza
flu starts every year in SE asia and moves to the southern hemisphere for our summer
Moves to the norhtern hemisphere in November, and ouriwndter in roughly November to April
Inflenza Virus Genes
HA
HA binds to its receptor - sialic acid tipped galactose carbohydrates
NA cleaaves sialic acid form the end of the receptor to allow newly formed viruses to escape
Influenza Virus genes
M1/2
Matrix protein1 (M1), M2 M1 coats the inside of the envalope M1 is the most important protein for the structure, assembly, and budding of the virus
M2 is found in small amounts in the envalope
Influenza virus genes
nucleoprotein
nucleoprotein which associated with the RNA segments
Polymerase B1, B2, and A
RNA pol subunits which transcribe and replicate the viral genome are carried into the host cell along with the genome
non-structureal 1 and NS2
regulation of genome replication and export of RNA-protein from the nucleus (NEP)
figure 22-17
Influenza symptoms
acute onset fever/ chills
headache, muscle aches
malaise
non-productive cough, shortness of breath
sore throat
lasting 3-7 days
Influenza entry into the cell
The influenza hemagglutinin binds to sialic acid containing glycoprotein receptor on epithelial cells.
viral particles are taken up by receptor mediated enfdocytosis and fuse with a lysosome
the drop in pH in the virus containing endosome causes a conformational change in hemagglutinin
Influenza entry into the cell
post pH drop in phagosome
after the conformational change of hemagglutinin, part fo the hemagglutinin is now exposed and can mediaate fusion between the viral envelope and the endosome mebrane
nucleocapsis are then liberated into the cytoplasm and move to the nucleus
Viral RNA is replicated in cell nucleus using viral encoded RNA-dependent RNA polymerase
10 transcripts produced, )+ sense mRNA)
Influeza trascripts
10 transcripts produced, (+ sense mRNA)
viral mRNAs “steal” the 5’ cap and 3’ poly A tail from preformed cellular mRNAs
viral proteins are synthesized
nuclear repliction of the original 8 (-) strand RNAs
assembly of new virus nucleocapsids
migration to cell membrane
budding out through the membrane
Influenza Antigenic shift
antigenic shift is caused by reassortment
=> two different types of flu viruses co-infect the same host
RNAs from both viruses are mixed together in a recombinant virus
the 957 pandemic virus (H2N2) was a recombinant of the previous human HN1
=> avian HA, NA, and Pb1. Other proteins are human flu viral
Influenza antigenic drift
antigenic drift is the frequent change to influenza virus
RNA viruses mutate faster than DNA viruses or cells
estimated at 7x10^-3 substitutions/site/year for the HA gene in influenza A
a mutation may change the conformation of the HA enough that antibodies to the WT do not bind
=> no protective immunity
Influenza strain nomenclature
a particular isolate is identified by type, host, species, geographical site of isolation, number and year
Influenza vaccines (egg)
influenza virus is injected into chicken eggs and replicates
virus is separated from egg components and purifed
virus dissociated by detergent treatment
purified HA and NA protiens are used in the vaccine (split vaccine)
=> there are also quadrivalent (4 strain) vaccines
Influenza vaccines (live attenuated)
live virus vaccines uses a cold-adapted strain
can be grown in culture at < 37C
replicated poorly in humans at body temperature but confers immunity
Influenza vaccines (cell-culture)
since 2012
based on madin-daarby canine kidney (MDCK) cells and vero cells
since 2019 in canada FLUCELVAX QUAD form seqirus
Influenza anti-virals
amantadine and rimantadine
=> only for flu A
=> no longer used (much) due to resistance
Oseltamivir, zanamivir, peramivir
=> for both A and B
=> neuaminidase inhibitors
Baxloxavir
=> inhibits RNA pol
=> inhibits “cap snatchin” of host mRNAs
Serotypes of rhinovirus
also known as enterovirus
A, B, C
about 160 different serotypes
virues that cause flu-like symptoms
corona viruses
6 other different types that cause symptoms
sars, mers, covid19
and 4 circulating corona viruses (seasonal)
rhinovirues
adenovirues
Rhinovirus transmission
airborne and direct contact transmission
2day incubation
infection of URT, temperature optimun 32C
Pertussis
also known as whooping cough
Bordetella pertussis
Gram-negative cocco bacillus
aerobic, oxidse positive, motile, encapsulated
humans or the only resivoir
pertussis transmission
airborne
7-10 day incubation
attachment and colonization of the tracheal and bronchial epithelialcells
filamentous heamagglutinin
fimbriae, petractin
pertussis exotoxins
produced at the site of infection
=> Pertussin toxin (PT), and A-B toxin kills cells and stimulates inflammation
tracheal cytotocin stops ciliary action of epithelial NK cells
Stages of a pertussis infection
catarrhal
=> moderate symptoms, runny nose, low fever, cough or sneezing but patient is highly infective
paroxysmal
=> sever, spasmodia coughing lasting several minutes, whooping sound as air inhaled
=> can fracture ribs or cause brain damage (2-4 weeks duration)
Convalescent stage
=> one week to several months
=> decline in coughing
complications of pertussis
bronchopneumonia
encephalopathy leading ot conulsions, brain damage and death
pertussis vaccination
heat kille dwhole cell caccine was introduced in the 1940s
concern over fatal reactions in the 1970s lead to the development of acellular vaccines based on pertussis toxin and filamentous haemafflutinin
usually combined with pertactin and type 2 and type 3 fimbriae
may be less effective over the long term
new genetically modified whole cell vaccines
Legionnaires disease
legionella pneumophila
aerobic, motile, Gram-negative coccobacillus
high fever, cough, shortness of breathg, myalgia, headaches
incubation 2-10 days
Legionnaires disease transmission
inhalation of airborne droplets
=> often from contaminated water such as humidifiers, hot tubs, water cooling towers
case-fatality rate of 10% and up to 25% with underlaying respiratory conditions
amoeba-resistnace bacteria (ARB), a new disease?
Human rhinovirus physiology
single-stranded positive sense TNA viruses (direct translation to proteins once in the cell)
genomes about 8000 nt in length
ath the 5’ end of the genome is a virus-encoded protein
3’ poly A tail
Virion about 30nm in diameter
=> smallest of ciruses, used to call them picornaviruses
Human rhinovirus symptoms
sore throat
runny nose, nasal
congestion
muscle aches, headache
fatigue, malaise, muscle weakness
lasts one to two weeks
starve a cold, feed a fever => not true
Temperature and Rhinoviruses
optimun temperature 32C
Many virues are much more sensitive to temperature that bacteria are
lowever temp in the extremities and upper respiratory tract
(note the temp of the lower RT is closer to 37 and thus they can really get down there)
Rhinovirus replicate in the nose, they get down the lower RT, but they dont replicate very well
temp a big factore
Viral respiratory diseases causig skin rashes
Transmitted by aerosols, infect through the RT
sytemic infections
Red facial rash spreading to body and extremities
pustular (skin raised to lump that break open) rash in chickenpox
Measles
RT infection that causes rash
long term immuno-suppression up to 4 months
can have case-fatality rates of up to 30% in cases with complications
used to the 4th highest cause of death in childern (infectious cause of disease) across the world. and this was in the 90’s when it was low (2million/ per in 80s) down form
long term immunosupression
