Micro Flashcards
1
Q
Classification systems for respiratory infections:
A
Site of infections:
- upper respiratory tract (URT)
- Rhinitis/ rhinosinusitis
- sinusitis
- otitis media
- epiglottis
- pharyngitis/Tonsilitis - Lower respiratory:
- Laryngotracheitis
- Bronchitis
- Bronchiolitis
- Pneumonia/ Pneumonitis
2
Q
Etiology of respiratory tract infections.
A
- Strict pathogen :
exogenous transmission cause primary infection such as virus - Opportunistic pathogen:
Endogenous microbes cause secondary infection.
3
Q
High risk gorups increased risk for severity of primary infections?
A
- Pre existing lung disease like asthma , copd, cystic fibrosis
- smokers
- immuno-compromised
-age (under 5 yrs, over 60) - Environmental risk like hospitalization, travel, seasonal
etc
4
Q
Individuals with……………………………. are at high risk of primary and seconary infections.
A
pre-existing lung conditions or intubation
- scar tissue &damaged cilia - binding site for opportunists!!
5
Q
How’s like innate host response to viral infection?
A
Interferon alpha and beta play a major role initially controlling viral infection,specificially inhibitng translation.
6
Q
Interferon alpha and beta creates…….
A
non-specific febrile disease like flu-like symptoms are result of type I interferons and t cell proliferation.
7
Q
How’s like adaptive host response to viral infection?
A
CD8+ CTL (cytotoxic lymphocytes) detects viral peptides in context of MHC class I and directly kill virus infected cells. CTL are able to kill virus infected cells by release of granzymes and perforin with assistance from CD4+T helper cells.
- CTL destruction of host cells cause collateral damage = symptoms
8
Q
Common cold virus
A
Rhinovirus,
Coronavirus
Adenovirus
9
Q
Rhinovirus … what season?
A
summer
10
Q
Coronavirus…. what season?
A
winter
11
Q
Adenovirus
A
all season
12
Q
naked virus — envrionmental surface infection meaning formite mediated transmission and survival in droplet. Which are?
A
Rhinovirus, adenovirus
13
Q
Rhinovirus is…..
A
Non-enveloped ss+RNA., icosahedral virus
labile at acidic PH meaning degradation in GI tract.
Family: Picornaviridae
14
Q
Epidemiology of rhinovirus?
A
Transmission is via aerosol, direct contact and indirect contact like nose to hand, hand to hand
- Most common
- immunity is transient due to antigenic drift
15
Q
Pathogenesis of rhinovirus?
A
VAP binds to host receptor ICAM-1 on respiratory epithelium of nares, oropharynx, throat.
- viral replication via ss(+)RNA genome to SS- RNA template via rna dependent rna polymerase. Viral replication triggers interferons, histamine and bradykinin, Replication is preferential to nose at 33 ‘C
- Contribution of host immune response like interferon alpha natural killer cells and cytotoxic lymphocytes
Infection is transient, self resolving and symptoms are primarily caused by immune response.
16
Q
Key point of pathogenesis of rhinovirus
A
IFN/ Bradykinin, bradykinin, histamine released leading to swelling, redness.
Interferon cause fever whereas histamine cause allergic symptoms.
- After reaction of immune response, around 3-7 days we have IGA antibody. = resolution of infection
17
Q
Clinical feature of rhnovirus?
A
- Onset 12-14 hrs. Resolution 7 days Watery eyes - nasal congestion -runny nose - sneezing - scratchy/ sore throat - dry cough - fever
18
Q
What is coronavirus?
A
- Family: Coronaviruidae
- linear, ss +RNA
- enveloped
- largest positive strand RNA viruses
- 2nd most common cause common cold
- peaks in winter
19
Q
What is adenovirus?
A
- Family: adenoviridae
- linear, ds DNA
- non-enveloped
- naked capsid has fiber with penton base (viral attachment protein)
- Immunity is transient (too many serotypes meaning variation)
20
Q
Features of adenovirus?
A
- Endemic throughout the year
- Affects all age, typically affects children from infancy to school age
- highly infectious
- military recruits
21
Q
Prevention of adenovirus….
LIVE oral vaccine against ……………
A
type 4&7 for military
22
Q
Epidemiology of adenovirus.
A
- pharygngo-conjuctival fever
- mild URTI - 3rd most common
- Interstitial pneumonia / ARDS
23
Q
Pathogenesis of Adenovirus?
A
- fibers protein attaches to CAR(Coxsackie- adenovirus receptor)
- penton base has cytolytic toxic activity
- Cell rounding, enlargement, intra-nuclear inclusion.
Intra-nuclear inclusion is feature of dna virus
24
Q
Clinical features of adenovirus: of pharyngo- conjunctivitis
A
- pink eyes
- onset 3-5 days
- resolution 10 days
- low grade fever
- swollen cervical lymph node
- sore throat
- itchy red eyes, often with clear discharge
25
Outcome and Prevention for viral URTI
-No vaccine for rhnovirus, and common coronavirus
- usually mild and self limiting illness
-severe complication not common (less than 10% secondary bacterial)
- Live vaccine for adeno (military)
- hand washing, hand sanitizer
- emphasize other environmental measures to control infection: avoiding finger to eye, finger to nose
mask wearing
social distancing
26
Epidemiology of sinusitis & otitis media:
- Both are common secondary infection following viral rhinitis
- Bacteria are common to oropharynx especially children and eldely, transient transmission by respiratory droplet. Think of it as trigger
- viral rhinitis increases inflammation triggering release of endogenous bacteria
- Children under 4 years will develop acute otitis media
27
What are the bacterial agents are common endogenous colonizers of nasal cavity and oropharyns, in persistent biofilm form?
- Streptoccous Pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
Chronic: staph aureus
28
What is streptococcus pneumoniae?
- Gram positive diplococcus
- Polysaccharide capsule
- a- hemolytic on blood agar
- optochin sensitive
- bile soluble
- positive quellung reaction : detect capsule
29
Prevention of S.pneumoniae?
1. Pneumococcal polysaccharide vaccine - inactivated vaccine
- purified capsular antigen of 23 serotypes
- adults 65 years or order
- Pneumovax 23
2. Pneumococcal conjugate vaccine
- prevnar 13
- children younger than 2 and adults
30
Pathogenesis of S>pneumoniae.
1 Initial infection: S.pneumoniae colonize epithelium of orpharynx and secrete IgA protease.
- persist asymptomatically in healthy host as biofilm
2. Virulence activation:
primary viral infection triggers inflammation.
- immunological stress disrupts biofilm, inducing release of pneumolysin (cytotoxin)
3. Contribution of host immune response
- resident macrophages recognize GPC with TLR2, releasing TNFa and IL-8. neutrophils are recruited.
- bacteria escape phagocytosis by capsule and can migrate to sinuses, eustachian tubes, inner ear, bronchi, alveolar sac, blood, meninges
31
Biofilm function
Bacteria bind to respiratory epithelium and establish a biofilm on respiratory epithelial cells, contributing to persistent colonization.
- Chronic biofilm is a risk factor for exacerbation in high risk patients esp. COPD.
32
Function of IgA protease
Bacteria secrete an Ig A protease to cleave mucosal IgA, contributing to persistent mucosal colonization.
33
function of pneumolysin?
When induced by immunological stress aka viral infection, bacteria secrete an Pneumolysin (exotoxin) which causes localized host cellular damage.
- cytotoxic for respiratory epithelial and endothelial cells.
34
S. Pneumoniae pathogenesis: Capsule
- capsule protects bacteria from phagocytes recognition via complement opsonization
- T independent B1 cells of spleen play important role to generate anti-Capsule IgM to activate complement for bloodstream infection.
SO, Asplenia is a major risk factor for bacteremia, sepsis, and meningitis with encapsulated bacteria.
35
Clinical features of sinusitis:
```
VIral UTRI <7 days
Bacterial URTI > 7
- fever
- nasal stuffiness and thick discharge
- bad breadth or loss of smell
-fatigue, headache
- postnasal drip
- sore throat
- viral = thin, clear discharge
where as bacteria has thick, yellow discharge
```
36
Clinical features of acute otitis media?
- fever
- neonates: irritability, feeding difficulties
- ear pain, and or ear tugging.
37
Clinical features of chronic otitis media?
- infection persist for more than 3 weeks
- ear pain
- hearing loss
- Air /fluid accumulation
MRSA is the most common cause
38
What is Haemophilus influenzae?
- Gram negative coccobacilli/ pleomorphic
- Non-typeable : non-encapsulated: normal component of Upper RT flora. Associated with sinusitis, otitis media, bronchopneumonia
- Typeable: capsule
Haemophilus influenzae type b (Hib)
- capsule composed of Polyribosyl- ribitol phosphate PRP
Prevention: Hib- PRP conjugated vaccine
Associated with epiglottis, sepsis, meningitis
39
Haemophilus influenzae does not grow?
on blood agar whereas it grows on chocolate agar
| - requires NAD &Hemin for growth
40
Pathogenesis of haophilus influenzae:
- Pili
- non-pilus adhesin
- biofilm
- IgA protease
- LOS: has endotoxic lipid A activity;; endotoxin .. recognized by macrophages and recruits of neutrophils- pus
HiB only, has capsule
41
Clinical presentation: epiglottis encapsulated Hib ONLY
- neck hyperextended, trunk forward(tripod) , enlarged epiglottis: Thumb sign
42
What is moraxella catarrhalis?
- gram negative diplococcus
- oxidase positive,
- colonize URT, particularly Children
- associated with sinusitis, otitis media, bronchopneumonia
- no capsule
43
Moraxella catarrhalis colony on
blood Chocolate agar solid colonies that can be pushed like hockey puck
gamma haemolysis
Haemo : no growth on blood agar
Strep . pneumo: alpha
44
Pathogenesis of moraxella catarrhalis:
- biofilm
| - LOS: induction of inflammation
45
Bacterial URTI: Outcome and prevention
- Often requires antibiotics fully resolve
- complication: tympanic perforation, chronic sinusistis, deafness abscess formation, penumonia , exacerbation of COPD.
- pneumococcal, Hib vaccines esp, infants and high risk
- antibiotic resistance is becoming more common.
46
What is Mumps?
- Paramyxoviridae family
- Enveloped ss_ RNA virion
- One serotype, endemic
- Aerosol transmission
- infection from crowded condition
47
What are the clinical presentation of mumps parotitis?
- Low grade fever, malaise, myalgia, headache, and anorexia.
- Parotitis may be unilateral or bilateral
- swelling of parotid and tenderness
- difficulty eating, swallowing, talking
48
What are the complication and prevention for mumps?
- Orchitis- most common complication after parotitis.
= inflammation of one or both testicles
- meningoencephalitis = inflammation of the the meninges (covering of the CNS) and inflammation of the brain tissues respectively.
- Most patients experience complete recovery with no long term effects
- Prevention : MMR/ MMRV vaccine
49
What is pharyngitis?
- inflammation of the pharygeal tissues, and tonsils usually associated with pain.
- characterized by triad of - sore throat, fever, pharyngeal inflammation such as edema, ertythema
-
50
Difference between viral pharyngitis and bacteria pharyngitis?
```
* Viral pharyngitis:
Gradual onset
low grade fever
Less erythema and swelling of the pharynx
Discrete ulcerative lesion
Tonsils generally not involved
```
- Conjunctivitis, coryza, cough may be present.
- an acute inflammatory contagious disease involving the upper respiratory tract = coryza
* Bacterial pharyngitis:
Acute onset
Sore throat, fever
nausea, vomiting and headache
erythematous posterior pharynx and palatine tonsils
tender cervical lymphadenopathy
white or yellow exudate in tonsillar crypts
51
What is S. pyogenes?
- gram positive cocci
- B hemolytic
-Lancefield group A
-PYR positive
-Bacitratin sensitive
-
52
Epidemioloy of S.pyogens?
Estimated to cause over 500 million cases of pharyngitis worldwide yearly
- most common cause of bacterial pharyngitis
- Humans are the primary reservoir: skin and throat
53
Clinical presentation of pharyngitis?
- Develops 2-4 days after exposure
- abrupt onset of fever, sore throat, malaise, headahe, dysphagia
- erythematous posterior pharynx and palatine tonsils
- tender cervical lymphadenopathy
- palatal petechiae
- tonsils may have white or yellow exudate
54
What is clinical features of scarlet fever?
- fever, headahce, sore throat, nausea, vomiting, and malaie
- diffuse, sandpaper- like rash, develops, initially on trunk and groin then spreads to face.
- accentuation of the rash in flexor creases
- Initially a thick, white coat and swollen papillae seen on tongue (white strawberry tongue)
- White coating desquamates leading to red strawberry tongue appearance.
55
Chronic tonsillitis &peritonsillar abscess
- Complication if initial infection is untreated , potentially due to drug resistance or carrier state
- Polymicrobial infection : Group A strep
Staph aureus
gram negative anaerobic rods
-
56
clinical features of peritonsillar abscess?
- Fever, dysphagia,
Severe throat pain
hot potato. muffed voice=obstructive voice
Trismus= restriction of motion of jaw
57
Pharyngitis leading to
acute rheumatic fever.
58
What are the clinical features of acute rheumatic fever?
```
Fever, polyarthralgia
caroditis
polyarthralgia=
Erythema marginatum
susbcutaneous nodu
```
59
Diagnosis of acute rheumatic fever:
- evidence of preceding GABHS infection
| - clinical criteria like carditis, chorea like irregular movement, erythema marginatum, subcutaneous nodules, arthritis.
60
Pharyngitis leading to
```
PSGN..... post strep gramerulnephritis.
- acute nephritic syndrome
- hematuria
gross hematuria
- edema : protein loss
- hypertension: water retention
type III hypersensitivity.
```
61
What is corynebacterium diphtheridae?
- Genus: Corynebacterium
- Gram positive rods
- Non- motile, non spore forming
- aerobic
- club shaped plemorphic
- Only strains harboring phage- encoded toxin can cause disease.
62
Epidemiology of C. Diphtheriade?
- immunization rates are high
- humans are the primary reservoir
- trasmitted by droplet spread, direct contact
63
Pathogenesis of C.diphtheriade?
- organism is non invasive disase is due to local and systemic effects of the toxin
- Virulence factor= diphtheria toxin
- genes for toxin acquired via lysogenic conversion -bacteriophage
- DT is an A-Btoxin that acts in the cytoplasm to inhibit protein synthesis irreversibly
- causing the necrosis and inflammation, forming an adherent , leathery pseudomembrane.
64
continued of pathogenesis of C.diphtheriade
- Binding mediated by the B subunit
-A subunit moves into cytosol and goes to its target,elongatio factor 2
A subunit inactivates EF-2 by ADP ribosylation - shuts off protein synthesis - cell death.
65
Clinical presentation of c diphtheriade?
- Usually manifests as pharyngitis or tonsillitis
- malasise, sore throat and fever
- extensive lymphadenopathy bull neck
- Complication: carditis, nerve damage
- intact pseudomembrane on palate, tonsils or pharynx
66
complication and prevention for C.diphtheriae
- Complication due to systemic effects of toxin
myocarditis and nerve damage
- prevention: Dtap vaccine(Td or tdap)
67
Tinsdale agar
| - Elek test
C. Diphtheriade
- agar contains L-cysteine and sodium thiosulfate that are H2S indicators.
- Potassium tellurite is selective agent
- Elek test is functional assay to determine if clinical isolate has phage and is secreting toxin.
68
What are the examples of Lower respiratory?
- Laryngotracheitis
- bronchitis
- bronchiolitis
- pneumonia/ pneumonitis
69
What is Bordetella perussis?
- gram negative coccobacillus
- Regan lowe, Bordet- Genou agar
- Charcoal blood agar , samples acquired from ciliated nasal epithelium
70
Epidemiology &prevention for B.pertussis?
- very contagious
- Neonates &unvaccinated children less than 5 yrs of age
- asymptomatic carriers
- acellular pertussis DTAP/Tdap vaccine
- Recommended for infants
- tdap booster strongly recommended for pregnant woman to prevent transmission from mom to neonate
71
Pathogenesis of B. pertussis?
- Filamentous hemagglutinin , pertactin, fimbraiae facilitate right binding to ciliated epithelium of nose, trachea, bronchi.
- Colonization impairs ciliary function
- Bacteria secrete Tracheal cytotoxin and pertussis adenylyl cyclase toxin (alters GCPR signaling pathways)
- Cilia damage contributes to necrosis
- Leukocytes fail to migrate to infected tissue(leukocytosis)
- Excessive mucus production contribute to cough severity
72
Pertussis toxin.
- A-B type exotoxin, inactivates a subunit GCPR via ADP ribosylation
- inhibits immune signaling and chemotaxiss
Adenylyl Cyclase Toxin: Increases cAMP levels of respiratory epithelium
- contributes to immune cell dysregulation and increased mucus production
73
Clinical features of B. pertussis: whooping cough aka trachebronchitis.
- stage 1:Catarrhal
: Common cold/ rhinopharyngitits
-Stage 2: partoxysmal : Sore throat, intense coughing, epsides followed by a whoop, productive clear sputum , predominant lymphocytosis
Stage 3: Convalescence: Residual cough.
Cough >14 days
74
- Paramyxoviridae family biology:
- Enveloped negative ssRNA genome
-PIV: Parainfluenza virus
- Respiratory syncytia Virus: RSV
- Human MEtapnemovirus (HMV)
, - measels virus
Mumps virus
75
Parainfluenza PIV epidemiology:
- 4 serotypes
- children <5 yrs old
- predisposing factors: Asthma, vitamin A deficiency, lack of breastfeeding, Environmental smoke or toxin
76
EPidemiology of parainlfuenza
CROUP (Laryngeotracheobronchitits)
77
Pathogenesis of PIV:
- HN on virion acts as VAP; binding to host receptor sialic acid on respiratory epithelial cells
- Fusion F protein has a hydrophobic fusion pepetide which is exposed after VAP attaches
- F protein inserts into host membrane, triggering fusion of virion and target cell lipid bilayer membranes.
78
pathogenesis of PIV
- Viral replication leads to surface expression of F protein , leading to fusion to new cells aka : Syncytium formation.
- Viral replication, syncytia and host response trigger inflammation for lining laryns, trachea, and bronchi
79
Clinical features of PIV:
```
Croup: Laryngo tracheo bronchitits
- inspiratory stridor : whistle
Subglottic narrowing of the treachea: steeple sign
- Barking cough
- hoarseness
```
80
RSV epidemiology:
- leading cause of LRTIs in infants and young children
| - infans <6 months or premature birth (<35 weeks)
81
Pathogenesis of RSV:
G protein mediate attachment; F protein mediates fusion
- virion directly invade the respiratory epithelium, leading to syncytia formation, which is followed by immnologically- mediated cell injury
- necrosis of the bronchi and bronchioles leads to the formation of plugs of mucus, fibrin, and necrotic material within smaller airways.
- infection can progress to alveolar sacs or trigger bacterial secondary super infections
82
RSV ;
necrosis, inflammation and syncytial giant cell formation!!
83
Clinical presentation of RSV:
- Bronchiolitis- interstitial pneumonia
- respiratory distress(RR, retraction and wheezing)
- atelectasis
- hypoxia, cyanosis
Chest radiograph : of an infant with a severe case of Respiratory syncytial virus penumonia and bronchiolitis .
84
Human metapneumovirus HMPV and RSV
Family: Paramyxoviridae
| - confirmatory differential diagnosis requires RT- PCR
85
Bronchitis: outcome and prevention
- 90% bronchitis is viral and does not require antibiotics
- antibiotics for whooping cough will shorten the course
- complication include interstital pneumonia (especially infants) exacerbation of asthma and COPD, bronchiectasis, rib frature
Prevention and patient education:
- TDAP/Tdap vaccines, esp for infants and pregnant women
86
Pneumonia classification:
- typical
- atypical
Typical: gram positive and gram negative bacteria
Atypical: viruses, atypical bacteria, fungi, parasites
Exposure:
- community acquired pneumonia: no recent hospitalization
- nosocomial: Hospital acquired pneumonia:>48 hrs post- admission
- ventilator associated Pneumonia: >48 hrs intubation
- Pathology:
- broncho-pneumonia/ lobar: typical pneumonia with focal densities (alveolar sac or multipic alveolar sacs called lobar) CONSOLIDATION
- Interstital: atypical pneumonia with diffuse, hazy infiltrates (viral , atypical )
- if infection looks so bad- necrosis
87
Covid 19
actute (less than one month)
, community acquired,
interstital (hazy infiltrate)
viral tested by Rt-pcr
88
What is Sars- COv2?
Enveloped ss +RNA virus
- spike protein = vaccine
- RDRP-antivirals
Diagnosis: Rapid antigen elisa, lateral flow
Rt- PCR,
Serology-
89
Epidemiology and transmission of Covid 19
- aerosol droplet, airborne
- high risk populations for severe disease
- unvaccinated 97x risk of death
- elderly, hypertension, obesity, diabetes
- prevention: moderna, fpfizer: mrna subunit vaccines encoing spike protein
-
90
Epidemiology : shift versus drift
1. Drift: gradual accumulation of random point mutation
| 2. Shift: sudden phenotypic change of virus from gene rearrangement with co-infection with 2 strains.
91
pathogenesis of SARS- COV2
1. Spike protein binds to ACE2 host receptor on epithelial cells of URT and LRT and or GI tract
2. Virus downregulates interferon - alpha
viral replicates in interstitial tissue, syncytia formation
virions spread systemically replicating in CD4+ T cells, cardiac, hepatic, renal tissue.
3. Inflammatory dysregulation and cytokine storm - causing inflammation
- alterationn of renin- antiotension signaling activates bradykinin.
Vascular damage accumulates on major organs.
detrimental causing inflammation, if it gets to lung ,oxygen exchange problem.
92
clinical presentation : covid 19
1. Non- specific URTI symptoms. , loss smell(anosmia), loss of taste( ageusia)
2. Interstitial pneumonia progressing to acute respiratory distress syndrome ARDS is most common cause of mortality.
3. if it gets into blood, immune- mediated inflammation can cause multi organ tissue damage
93
imaging for covid -19,
ground glass opacities are most common.
| consolidation can be observed.
94
Complication for covid-19
1. intersittial pneumonia- ARDS- death
2. Secondary bacterial pneumonia superinfection
3. long COVID
95
What is influenza?
1. Orthomyxoviridae
- enveloped segmented ss negative RNA
- Hamagglutinin glycoprotein (HA)= viral attachment protein
- Neuraminidase (NA ) surface enzyme- release of new virions by sialic acid cleavage
Three types :A,B , and C
- based on Matrix (M-protein) and nucleoprotein
Rapid antigen test can determine type A/B
96
Biology for inlfuenza:
1. HA- attachment
Hemagluttanin binds to the sialic acid. (restricted to respiratory tract)- it doesn't fusion so no syncytia
2. NA- release neuraminidase cuts sialic acid.
M2- uncoating
97
Epidemiology &transmission for influenza:
1. Three types:A,B,C
Type A: Zoonotic:
More pathogenic than B and C
Reservoir: humans, birds, swine, horses, seals
- Antigenic shift : causes pandemic (Swine flue)
- Antigen drift: cause localized annual epidemic
Type B, and Type C : are human restricted cause milder symptoms and undergo antigenic drift only!!
Transmission : aerosol droplet - human to human, animal to human.
98
Influenza type A H1N1 is
has tropism for humans, pigs, horses, and ducks.
99
Influenza shift epidemiology:
- Flu pandemic are result of cross species shift events.
| - The global swine flu pandemic in 2009 resulted from genetic reassortment.
100
prevention for influenza virus
1. prevention annual drift necessitates yearly booster
- Live, attenuated nasal spray: Induces strong IgA response. Recommended for > 2yrs , <50 yrs
- Killed, inactivated shot : induces IgG response
- recommended for health are worker, Age extreems, immunocompromised.
101
Pathogenesis of influenza virus
- Influenza HA targets sialic acid on mucus secreting, ciliated cells and replicates in respiratory tract
- Infection in lower respiratory tract leads to cytokine storm and desquamatin of bronchial epithelium cells
- virus infection facilitates primary viral pneumonia and onset of secondary bacterial infection
102
Clinical features: the flu
Preceded by or with a cold
- dry sputum cough
- dyspnea
- high fever
- intense muscle pain
103
Complication of influenza:
" Secondary bacterial superinfections including sinusitis, otitis media(children), typial bacterial pneunmenia(elderly) - most common
104
Complication of COvid-19 and flu
Covid -19: ARDS, sepsis, multi-organ damage
Flu: post- flu bacterial pneumonia, ARDS
Approximately 1/3 COVID-19 patients experience symptoms for months
- Annual influenza vaccines(attenuated spray, killed shot)
- SARS- COV2 subunit vaccines
105
What are the typical pneumonia: risk factors ?
underlying lung disease or compromised muco-ciliary function - risk of bronchopneumonia especially smokers, COPD/CF, alcoholics, ventilation.
- preceding viral infection (trigger)- risk of secondary superinfection.
- Suppressed immune system - risk of bacteremia and meningitis with encapsulated bacteria esp. asplenia
- Risk of sepsis with S.pneumoniae is 500x higher in children with sickle cell compared to healthy children.
106
Typical pneumonia: gram positive and gram negative
- Streptococcus pneumoniae is most common for community- acquired
- Drug resistant gram-negative baclli are common for hospital acquired.
107
Bacteria pneumonia distinguished into
1. Bacterial typical pneumonia
| 2. Bacteria atypical pneumonia
108
What are the bacteria are in bacteria typical pneumonia?
1. community acquired: Strep pneumoniae - gram positive diplococci, alpha, quelling, optochin positive
- Haemophilus influenzae (gram negative coccibacillli)
- Moraxella catarrhalis- gram negative cocci, oxidase
- Klebsiella pneumoniae- gram negative bacillus
2. Hospital acquired- staph aureus MRSA - gram positive cocci , catalase +, beta
- Klebsiella pneumoniae- gram negative bacillus, lactose fermenter
- Pseudomonas aeruginosa- gram negative bacillus, lactose non-fermenter
109
What is Klebsiella pneumoniae?
- Family: Enterobacteriaeceae
gram negative bacillus, prominent capsule
- lactose fermenter (macconkey agar- big capsule)
In the sputum sample: gram negative with capsule
- capsule bacteria can lead to sepsis
110
What is epidemiology of Klebsiella?
- Part of microbial flora (intestine)
- asymptomatic carriage if bacteria remains in colon
Community acquired , aspiration - chronic alcohol abuse
- hospital acquired, ventilator associated- intubated COVID patients
111
Pathogenesis of klebsiella?
1. LPS(Endotoxic effect of LipidA)
- Triggers robust inflammatory response via TLR 4 signaling (IL-8, TNFalpha leads to neutrophil recruitment)
2. Capsular polysaccharide- K antigen
- Anti-phagocytic, immune evasion contributes to progression from pneumonia to sepsis
3. MDR (multiple drug resistant) plasmid- highly mobile passed by horizontal gene transfer
- extended spectrum- beta lactamase ESBL - Klebsiella
- Carbapenemase CR- Klebsiella or CR0 enterobacteriaceae
112
Klebsiella pathogenesis: Aspiration pneumoniae(subset of typical pneumonia with high mortality) ?
- microbes originate from GI tract, and aspirated in patient with loss of gag reflex ex vomiting CAP or intubation HAP.
- >1 area of lung parenchyma replaced by cavities filled with debris.
- putrid odor to breath and sputum
- Large % of cases are polymicrobial and can progress o lung abscess formation.
* facultatitve anaerboes eat all the oxygen and allowing growth of anaerobes(gram negative anaerobic Roods with GNAR, ex0 bacteroides)
113
clinical presentation for typical pneumonia/ lobar bbronchopneumonia?
- productive cough, sputum is thick, viscous due to high neutrophil influx.
- dyspnea
- hemoptysis!! - S. Pneumoniae- rust colored sputum
- Klebsiella- current jelly sputum
- high fever
- signs of sepsis: tachycardia, hypotension, edema
Rapid onset of hours to days
114
typical bacterial pneumonia:
inflammation progresses esp. virulent, drug resistant bacteria (getting worsen X ray)
- Strep pneumoniae, MRSA
- Klebsiella pneumoniae, psedomonas aeruginosa.
- Bronchopneumonia- lobar consolidation- necrotizing abscess
115
Acute exacerbated chronic bronchitis AECB epidemiology &etiology
Subset of typical bbacterial pneumonia in patient with pre-existing cough
- Patients with COPD and cystic fibrosis are very high risk categories for bacterial LRTI
- bacterial agents are chronic endogenous biofilm colonizer of oropharynx and bronchi, exacerbation of symptoms are often triggered by viral infection.
- Patients should get routine pneumococcal vaccination!!
116
Streptococcus pneumoniae, NTHi, and Moraxella are “normal” benign colonizers in the nasopharynx, especially in the pediatric population. In a healthy host, these bacteria will remain senescent in biofilm form indefinitely. They will not have the inherent ability to gain access to the lungs as our muco-ciliary escalator and mucus will prevent any attachment or colonization below the trachea in a healthy person.
Pseudomonas is not considered a highly representative species for our respiratory mucosal tissue and it is strictly dependent on opportunities in a person with depressed defenses, ESPECIALLY persons with Cystic Fibrosis. The excessive mucus production in a relatively “sterile” environment of the bronchi is beneficial to Pseudomonas colonization; whereas, the normal flora in the URT will always out complete Pseudomonas.
Of note, Pseudomonas can cause soft tissue disease in healthy host such as hot tub folliculitis or swimmers ear aka otitis externa, but it will almost always be in context of exposure to water.
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Pseudomonas Biology
- Gram negative rods
- Lactose Non-fermenter, oxidase
- produces mucoid green colonies (pyocyanin) on conventional agar
- lung infections produce fruity smelling, yello green sputum
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Epidemiology of pseudomonas
- Opportunistic pathogen, dependent on altered host immune status
- pseudomonas is leading cause of mortality in CF patients
- At risk: COPD and CF
- ventilator associated VAP superinfection in COVID-19 patients
- Complication: Untreated or drug resistant VAP or AECB can progress to necrotizing bronchial pneumonia, sepsis and meningitis.
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clinical presentation : acute exacerbated chronic bronchitis AECB aka complicated Bronchopneumonia
1. Sudden onset of worsening of symptoms
2. Dyspnea
3. High fever
4. Productive sputum with abundant neutrophils
Sputum cultures are often poly microbial
- Biofilm with pnenumococcus, pseumonas, NTI, Moraxella
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Atypical pneumonia:
Agents are not visualized by gram stain or cultured on blood agar
Mycoplasma pneumoniae
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What is mycoplasma pneumoniae?
- pleomorphic, lacking cell wall
- due to lack of cell wall: resistant to Betalactam antibiotics.
- does not gram stain, requires NAAT
Cold- agglutinin test is screening tool
- fastidious, requires special media with sterols.
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Epidemiology of mycoplasma
1st MCC atypical bacterial CAP community acquired penumonia
65 , asthma is high risk
Outbreak lasting months occur in crowded institutional settings. Slow presentation!!
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Pathogenesis of mycoplasma?
- P1 adhesin= attachment organeele
- attaches to and damages the respiratory epithelial cells at the base of the cilia,
- produce hydrogen perioxide and cytotoxin for localized inflammation.
- molecular mimicry induces production of cross reactive antibodies (cold agglutinin reaction), associated with extrapulmonary complication.
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Clinical presentation: atypical pneumonia aka WALking pneumonia
- gradual and insidious onset of several days to weeks.
- dry persistent cough
- pleuritic chest pain
-shortness of breath
- fever, usually low
- headache, myalgias, arthralgias
;mild form of pneumonia
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What is bacillus anthracis
- gram positive rod
- inhalation of spores Wool sorter's disease
- pulmonary anthrax
Widened mediastinum
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Outcome and prevention for bacteria pneumonia!
Prognosis: typical : usually serious and may require hospitalization
atypical: can sponetaneously resolve
Complication ARE common: ARDS, pulmonary edema, abscess, sepsis
Multiple antibiotic resistant
Prevention: vaccines are available for S. pneumoniae
chronic colonization is common in COPD.
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What is mycobacterium tuberculosis?
- Acid fast bacilli
- strict aerobe
-catalse and SOD positive
Thick lipid rich cell wall
- mycolic acid and cord factor
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M. tuberculosis epidemiology and prevention?
- Endemic region esp SE Asia m Sub saharan afrian
- children more likely to present Primary active
- immunocompromised at high risk of reactivated.
Prevention: BCG vaccine
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M.tuberculosis epidemiology: HIV
- MTB- HIV co infection has very poor prognosis if person has subsequently developed AIDS immunosuppression
- MCC of mortality in persons living with HIV.
50-70% AIDs patient develop extrapulmonary TB infection
- disseminated infection can occur in any tissue
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Pathogenesis of primary:
- bacteria gain access to the alveolar sacs and bind C3b on cell wall, enhancing opsonization,.
- REsident alveolar macrophage engulf MTB.
- MTB modifiy phagosomal compartment to replicate intracellar.
- Prevent oxidative burst & inhibit phagosome- lysosome fusion (cord factor/ mycolic acid)
- Macrophages secrete IL-12 &TNF-alpha triggering local inflammation.
- TH1 cells, secrete robust amounts of IFN-y
- Activated macrophages, Th1 ,PMNs(neutrophils), surround infected macrophages.
- Healthy individuals form microscopic granuloma - latent
But patients with low CD4+ fail to control infection, forming larger granuloma(Ghon focus).
- cytokines and PMNs contribute to DTH (delayed hypersensitivity) tissue damage.
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M. Tuberculosis pathogenesis of re-activated:
- Live bacteria remain dormant in granuloma
- Reduction of CD4+ T cells destabilizes encased granuloca
- MTB begins replicating
- Bacteria preferentially migrate to lung apex(high oxygen)
- macrophage attempt to form granuloma , fail without Th1 - IFN-y
- Extensive host mediate tissue damage result in cavitation and extensive necrosis
- damage to vascular barrier can result in dissemination of MTB
- Infection overwhelms host
-
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Clinical presentation: active pulmonary tuberculosis:
- dyspnea, productive cough, sputum can be scant, clear or bloody,
- primary- mid lung, reactivated- apex, miliary- dispersed
- anorexia and weight loss
- slow onset weeks to months
- symptoms correspond to affected organ
- cancer like wasting
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diagnosis of M. Tuberculosis:
microscopy of sputum (bronchoalveolar lavage ) or tissue biopsy:
Ziehl-Neelsen stain
Rhodamine0auramine fluorescent stain higher sensitivity
`
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Cuture for M.tuberculosis diagnosis:
- Lowenstein Jensen medium
| - Antimicrobial susceptibility testing= increasing importnat
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TB skin test
Tuberculin Mantous PPD test: prior exposure to MT will result in delated type 4 hypersenssitivity DTH reaction
- doesn't differentiate active/latent TB or previous vaccination
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Quantiferon &ELispt: m
more senstivie in vitro immunoassays to detect MTB - specific memory CD4+ T cells.
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Difference between TB and Nocardia asteroides?
TB : Acid fast bacilli
| Acid fast filamentous : nocardia.
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Fungal infection especial fungal RTI
1. Primary pathogens: histoplasma capsulatum
- blastomyces dermatidis
- coccidioides immitis
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General features of primary fungal mycoses:
- high percentage are asymptomatic
| - if symptomatic, community- acquired pneumonia
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Pathogenesis of systemic fungal mycoses:
1. Initial infection: exposure via inhalation, fungal attachement, dimorphic conversion and or extension of hyphae
2. Virulence factor:
Incomplete killing of inhaled conidia- germination
- tissue invasion
- enter bloodstream and disseminate
3. damage results from : inflammatory response, direct damage to tissues, fungal enzymes
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Lab dianosis of fungal mycoses:
- sputum, bronchoalvolar lavage, transtracheal aspirate, lung biopsy.
-
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clinical features of histoplasmosis:
- Acute syndrome: pneumonia, disseminated disease (immunocompromised inidividuals)
- diverse range of presentation: asymptomatic
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Histoplasma capsulatum:
H.capsulatum var capsulatum - pulmonary &disseminated infections, eastern US &Latin america
0 thinner cell walls
H.capsulatum var duboisii- skin and bone lesison, tropical afria, thick walled
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BIology of histoplasmosis:
- In the environment, Histoplasma capsulatum exists as a mold with aerial hyphae. The hyphae produce macroconidia and microconidia and spores that are aersolized and dispersed.
3. The warmer temperature inside the host signals a transformation to a oval, budding yeast. 4. The yeast are phagocytized by immune cells and transported to regional lymph nodes. 5. From there they traveled in the blood to other parts of the body.
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Epidemiology of Histoplasmosis:
Most common endemic fungal infection in humans
- Fungus naturally found in acidic soil with high nitrogen content- enriched with bird or bat droppings.
- Outbreak therefore associated with - areas where birds/bast roost, caves old buildings.
Pathogenesis: microconidia and hyphae are aeroslized and inhaled.
- phagocytized by alveolar macrophages.
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Histological finding for Histoplasma capsulatum:
non-encapsulated, thick walled and narrow base budding yeast in alveolar macrophages. (facultatively intracellular)
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Clinical features of blastomycosis:
- Acute: illness resembles bacterial pneumonia, with mucopurluent or purulent sputum
Chronic: resembles TB(low fever, cough , fatigue, chest pain, night sweats)
- Cutaneous lesion are the most common extrapulmonary form : verrucous or ulcerated in appearance.
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Biology of blstomycosis:
- in the environment, Blastomyces exists as mold with septae aerial hyphae,. The hyphae produce spores. These spores are either inhaled or inoculated into the skin. The warmer temperature inside the host signals a transformation into a broad based budding yeast. The yeast may continue to colonize the lungs or disseminate in the bloodstream to other parts of the body, such as skin, bones and joints, organs and other CNS>
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Epidemiology of blastomyces dermatitids:
- soil, decaying organic material : not usually associated with exposure to bird or bat droppings.
- outbreak associated with contact with disturbed soil
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Histopathological findings for balstomyces dermatitidis:
broad base budding yeast
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clinical presentation: coccidioidomycosis(valley fever)
- Primary ccoccidioidal pneumonia:
1. resembles a community acquired pneumonia- cough chest pain, fever
2. Genralized systemic symptoms: fever drenching night sweats, weight loss,
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Pathogenesis of coccidioidomycosis:
In the environment, coccidioidomycosis exist as a mold with septae hyphae. The hyphae fragment into arthroconidia which measure only 2-4cm in diameter and easily aerosolized when disturbed. 3. Arthroconidia are inhaled by susceptible host. 4 and settle into the lungs. The new environment signals a morphologic change, and the arthroconidia becomes spherules. Spherules divide internally until they are filled with endospores When a pherule ruptures the endospores are released and disseminate within surrounding tissue. Endospores are ten able to develop into new spherules and repeat the cycle.
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Coccidioides : valley fever
| Epidemiology:
```
dry season (following rainy season)
Pathogenesis: inhalation of arthroconidia
after inhalation, enlarge into barrel shaped spherules.
```
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Clinical presentation: paracoccidioidomycosis:
2. chronic form : reactivation of primary infection
more common form.
Paracoccidioides brasiliensis
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Opportunistic fungal pathogens: -
1. cryptococcus neoformans
2. Pneumocystis jirovecii
3. Aspergillus spp.
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Who do these opportunistic fungal infection occur in?
1. crytoccocus neoformans
2. penumocystis jirovecii
3. Aspergilus spp.
Immunocompromised individuals including
- malignancies, bone marrow transplantation, solid organ transplantation on immunosuppressive treatment, prolonged corticosteroid therapy.
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Clinical presentation: cryptoccocus:
- India ink prep: polysaccharide capsule is clear halo around yeast cells.
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cryptococcus neoformans: encapsulated yeast
Epidemiology: grows well in decaying wood, soil especially soil enriched by bird dropping.
- common fungal infection inAIDS patients with CD4+tcell count less than 100
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Pathogenesis of cryptococcus neoformans:
- inhalation trigger production of capsule
| - strong affinity for CNS - neurotropic
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Pneumocystis jirovecii
- has cholesterol in place of erogsterol in cell wall.
| - common fungal infection in AIDS
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Aspergillus sp:
- septae hyphae, acute- angle branching
- Afumigatus
decaying organic matter, air and soil
pathogenesis: inhaled conidia are phagocytosed.
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What is atypical clinical features?
- gradual and insidious onset
- milder symptoms compared to typical pneumonia:
fever with chills, shortness of breath, dry to mildly productive cough , headache, myalsgias, arthralgias, loss of appetitie, low energy, and fatigue
- mild pharygeal injection, skin rash (mycoplasm)
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Community Acquired Pneumonia (atypical)
: Mycoplasma pneumoniae
- chlamydia pneumoniae
- legionella pneunophila
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What is Legionella pneumophila:
- clinical syndrome:
- legionnarire disease
- pontia feer
- gram negative rod, motile, non spore forming
- cultured buffered charcoal yeast extract agar.
Look for GI/ CNS involvement along with respiratory disease plus water
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Pathogenesis of Legionella pneumophila:
- exposure= inhalation of contaminated aerosols
- facultatively intracellular (alveolar macrophages)
- prevent fusion of phagosomelysosome
- virulence factors: intracellular growth
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factors increase the risk of infection (legionella pneumophila)
- Decreased local or systemic cellular immunity
- activates that increase the chances of exposure to an infectious of contaminated water.
- Environmental and bacterial factors
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Diagnosis and laboratory testing for legionaries disease?
- GI and CNS symptoms
- hematuria
- hyponatremia
- elevated hepatic transminases. \
- most commonly used laboratory test for dianosis is the urinary antigen test.
- Methlyamine silver staining for lung tissue.n
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What is chlamydia pneumoniae:
- outer cell wall resembles G negative , weakly endotoxic LPS , lacks peptidoglycan
Major outer membrane protein
- common to all chlymydia and unique to each species
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Life cycle of chlamydia:
- Elementary body attaches to surface of cell,
endocytosis of EB occurs
, EBis in endosome which does not fuse with lysosome. -EB reorganizes into reticulate body in endosome
- RB replicates by binary fission.
-RBs are reorganized to EBs
- Inclusion granule has both RBs and EBS
- C. pneumoniae and C trachomatis: reverse endocytosis.
- C. psittaci: lysis of cells.
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Replication for chlamydia:
- Intact EB outer membrane inhibits fusion to the lysosomes thus no killling of Chlamydia.
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Chlamydia pneumoniae:
- school aged children, obligate intracellular, gram negative, diagnosis: PCR, culture, no special risk groups.
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What is ornithosis: chlamydia psittaci:
- obligate intracellular bacteria
| - birds are the natural reservoir
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Ornithosis: chlamydia psittaci pathogenesis:
- transmitted to humans through inhalation of excreta urine or respiratory droplets of birds
-
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High risk groups of clamydia psittaci:
- veterinarians, zookeepers, pet shop owners, employers of poultry processing plants.
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Clinical features of chlamydia psittaci:
- headache, high fever, chills. myalgia
- nonproductive cough and consolidation
- CNS involvement
GI symptoms
Diagnosis by serology.
- antibiotics
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What is hantavirus pulmonary syndrome:
- cluster of deaths in the southwest US
| - four corners disease
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Biology and epidemiology of hantavirus:
- RNA virus, spherical , lipid envelope with 2 major glycoproteins.
- Sin nombre virus- commonest cause of HPS>
- 96% reported cases of hantavirus pulmonary syndrome in states west of Mississippi river
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Hanta virus pulmonary syndrome:
rodents carry hantavirus primarily rats mouse.
- rodents infestation is priamry risk for virus exposure
- Cases of HPS occur sporadically, usually in rural areas.
- Peridomestic settings, barns, outbuildings, and sheds are potential sites.
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Disease transmission for HPS:
Rodents shed the virus in their urine, droppings, and saliva
- virus is mainly transmitted to humans when they breathe in air contaminated with the virus- airborne transmission
- HPS occurs in the fall
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Pathogenesis of HPS:
- generalized increase in capillary permeability that results from endothelial damage
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Clinical features of HPS:
- divided into 3 clinical phases
: 1. prodromal - resembles viral illness
2. Cardiopulmonary: dyspnea, dry cough
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What is melioidosis, AKA whitemore's disease?
| - infection caused by burholderia pseudomallei
Endemic regions are South Asia, SE asia including China, northern austrailia.
- gram negative bacterium, rod shaped, found in soil and fresh water.
- transmission: percutaneous inoculation, inhalation, aspiration
- common in rainy season
- Risk factors: cystic fibrosis
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Clinical features of melioidosis:
- Infection can be acute and chronic infection
- latent infection with reactivation like tuberculosis
- most common clinical manifestation: localized skin infection
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Lab diagnosis of melioidosis:
- Sputum culture
| : cornflower head morphology
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Lab diagnosis of melioidosis:
- cultue is the mainstay of diagnosis
- Ashdown's agar (selective media)
- Gram negative bacilli, bipolar staining.
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Prevention of melioidosis:
- Avoid direct contact with soil and standing water if risk factors present and in endemic region
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Q fever: Coxiella burnetii
Zoonosis
Coxiella burnetii
- Obligate intracellular organisms
- Cattle, sheep, goats are improtant reservoirs
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3 main clinical presentation of Q fever
- self limiting flu like illness
- pneumonia
- hepatitis
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Chronic Q fever:
sometimes present years after primary infection, culture negative endocarditis
- risk groups: pre existing heart defects
- pregnancy, immunocompromised
Diagnosis is seriological, phase I and II.
