Upper Respiratory Treact Infections Flashcards
1
Q
Upper Respiratory Tract
A
- Nose
- Pharynx
- Paranasal sinuses
- Middle ear
- Larynx
2
Q
URT
Normal Flora
A
Primarily coagulase-⊖ Staph and diphtheroids.
Colonization with Pneumococci, S. aureus, Moraxella, Haemophilus frequently present.
3
Q
URT
Sterile Sites
A
Sinuses
Middle ear
Larynx
4
Q
URT
Infections
A
5
Q
Pharyngitis
A
Acute inflammation of the throat ⇒ pain on swallowing and a red, swollen phryngeal mucosa.
-
50-75% caused by viruses and Group A Strep
- Adenovirus 25%
- Rhinoviruses 20%
- Group A Strep 15-30%
- Peak incidence is 3-18 y/o
6
Q
Otitis Media
A
Acute inflammation of the middle ear with fever and local pain.
- Purulent fluid accumulates behind a tense, red TM
- May discharge externally after TM rupture
-
Common in children < 3 y/o
- Most get 2-3/yr
- Frequently follows URT infection
- Most commonly caused by:
- Strep. pneumoniae
- Non-typable strains of Haemophilus influenzae
- Moraxella catarrhalis
- Treatment problematic d/t inc. abx resistance
7
Q
Otitis Media
Risk Factors
A
- Eustacian tube flatter and more narrow in children
- URT can trap fluids ⇒ colonization by normal flora
- Feeding tilts child into position where tube is flatter & more connected to OP ⇒ fluid can back up
8
Q
Otitis Media
Treatment
A
-
⅔ improve within 24 hours without abx
- 80% within 2-5 days
- Advise use of OTC pain relievers, anesthetic drops
-
Wait 24 hours before giving abx
- 24 months or older
- Otherwise healthy
- Mild sx or unclear dx
- Offer observation in 6-24 month olds
- Pathogens can cause meningitis ⇒ must monitor
9
Q
Otitis Media
Bacterial Pathogens
A
10
Q
Moraxella
Overview
A
- Moraxella catarrhalis ⇒ most important
- Related to Neisseriae
- Gram ⊖ diplococcus
11
Q
Moraxella
Transmission
A
- Transmitted by respiratory secretions
- Transient carriage/colonization normally
- Colonization of URT in 40-50% of school children
-
Endogenous infection
- Usually precipitated by URT infection
12
Q
Moraxella
Clinical Syndromes
A
- 3rd highest cause of otitis media and sinusitis
- Also causes bronchitis, PNA, and conjunctivitis
- Esp. the elderly, immunocompromised, or those with chronic pulmonary disease
13
Q
Moraxella
Diagnosis
A
-
Small, coffee-bean shaped gram ⊖ diplococci
- Likes to lie side by side
- Strict aerobe
- Oxidase ⊕
-
Does not ferment carbs
- Unlike Neisseriae
- Grows well on blood agar
- Prefers chocolate agar
14
Q
Moraxella
Treatment
A
~100% of strains are beta-lactamase producers
PCN resistant
Usually treat with cephalosporins
15
Q
Haemophilus influenzae
Characteristics
A
- Small, gram ⊖ rods (cocco-bacillus)
- Complex nutritional requirements
- X factor ⇒ hematin
- V factor ⇒ NAD or NADP
- Grows well on chocolate agar
- Grows poorly on blood agar
- Small satellite colonies grow around colonies of S. aureus or other factor V excreting organisms ⇒ satellite phenomenon
- ± polysaccharide capsules
- Classified based on capsule type ⇒ typable vs non-typable
16
Q
H. influenzae
Typable Strains
A
-
Encapsulated ⇒ Types a-f
- Typed based on antisera rxn to capsular polysaccharide
- HiB most invasive
- HiF incidence increasing
- Exogenous transmission
- Colonization uncommon
- ~5% of children
- < 0.5% of adults
- 1° pathogens ⇒ meningitis, bacteremia, epiglottitis
17
Q
H. influenzae
Non-Typable Strains
A
- Non-encapsulated
- Colonize 60-90% of children, 30-50% of adults
- Endogenous transmission
- Opportunistic ⇒ otitis media, sinusitis, pharyngitis, PNA
18
Q
H. influenzae
Transmission & Epidemiology
A
- Transmitted by respiratory secretions
-
Severe disease 1° in children 6-18 m/o and the elderly
- Ab levels lowest
- PRP polysaccharide is a T-cell independent Ag
- B-cell response to PRP poor under 18 m/o
- Systemic spread only typical for encapsulated strains
- Esp. HiB
- Bacteremia can lead to infection of CNS, bones, and joints
19
Q
H. influenzae
Virulence Factors
A
-
Polysaccharide capsule
- Antiphagocytic
- Blocks complement activation
-
IgA protease
- Avoids immune response at mucosal surface
-
Outer membrane proteins
- Attachment and adherence
-
Endotoxin
- Gram ⊖
20
Q
H. influenzae
Type B
A
- Most invasive strain
- Causes 90% of all H. influenzae infections
- Virulence due to unique polyribose-ribitol phosphate (PRP) capsule
- Contains pentose sugar
- ⊗ Phagocytosis
- ⊗ Alternative complement activation
- ⊗ Ciliary function
- Damages respiratory epithelium
- Penetrates epithelial and endothelial walls ⇒ dissemination
21
Q
H. influenzae
Clinical Syndromes
A
- # 2 cause of otitis media and sinusitis
-
Epiglottitis
- HiB only
- PNA
- Prominent in pts w/ underlying lung disease or debilitating conditions like malnutrition, lung CA, alcoholism
- Bacteremia
- Mostly encapsulated strains only
- Meningitis
- HiB only
- Usually follows URT infection
- Most common in unimmunized children 5 m/o-5 y/o
- More cases before vaccine available
22
Q
Acute Epiglottitis
A
- Caused by HiB only
-
Inflammed, swollen, cherry-red epiglottis
- Protrudes and obstructs airway
- Fever, sore throat, hoarseness, barking cough
- Can result in death due to suffocation if untreated
- Children < 6 y/o most at risk d/t smaller airways
- Local invasion ⇒ bacteremia ⇒ epiglottis
23
Q
H. influenzae
Lab Diagnosis
A
- Fastidious
- Specimen from NP swab, pus, blood, or CSF for smears and culture
-
Grows on chocolate agar or BAP with X factor (hematin/hemin) and V factor (NAD)
- Does not grow on normal blood agar
- PRP capsular Ag of HiB released into body fluids
- Antigen detection methods ⇒ latex agglutination
24
Q
H. influenzae
Immunity
A
-
Passive protection by maternal Ab
- No episodes until after 6 m/o
-
Opsonizing anti-capsular Ab
- Capsule-type specific
- Enhance phagocytosis by PMNs
- Bacteriolytic in presence of complement
- Active acquired Ab gradually increases up to ~ 10 y/o
25
H. influenzae
Treatment
* **Ampicillin for 5-10 days**
* **Some are beta-lactamase producers**
* ~ 25% of HiB
* Higher % of unencapsulated strains
* Varies with region
* **Via transmissible plasmid**
* **Newer cephalosporins are drugs of choice**
* Ceftriaxone, cefotaxime
26
H. influenzae
Prevention
* **Vaccine composed of PRP + diphteria CRM197 protein**
* **Immunization of infants at 2, 4, and 6 m/o**
* Greatly ↓ invasive disease esp. meningitis in young children
27
Bordetella
* **Cause infection of human tracheobronchial epithelium**
* **Bordetella pertussis** most important
* Causes **Pertussis** aka "Whooping cough"
28
Pertussis
Epidemiology
"Whooping Cough"
- 30 mil cases and 300k deaths per year worldwide
- 21k cases and 7 deaths in US in 2016
29
Bordetella pertussis
Characteristics
* **Gram ⊖ coccobacilli**
* **Strict aerobe**
* **Extracellular organism**
* **Fastidious and slow growing ⇒ takes 3-7 days**
* Requires specialized media
* Charcoal blood agar
* Bordet-Gengou agar (blood-potato-glycerol)
* Solely a human pathogen
30
B. pertussis
Transmission & Epidemiology
* **Exogenous transmission via respiratory secretions**
* **Highly communicable**
* Attack rate 90% in susceptible individuals
* Survives briefly outside of human respiratory tract
* **Infection most common in children \< 1 y/o & preterm infants**
* Esp. dangerous during first 6 months of life
31
B. pertussis
Virulence Factors
* _Adhesins_ ⇒ pili proteins that mediate attachment to ciliated epithelium
1. **Filamentous hemagglutinin (Fha)**
2. **Agglutinogens**
* _Toxins ⇒ cause cell and tissue damage_
1. **Pertussis Toxin (PT)**
* Major virulence factor
2. **Invasive adenylate cyclase**
* Enters host cell and ↑ cAMP levels
* Hemolytic
* Interferes with chemotaxis and superoxide production of PMNs
3. **Tracheal cytotoxin**
4. Hemolysin
5. Dermonecrotic heat-labile toxin
32
Pertussis Toxin
| (PT)
**Major virulence factor**
* **ADPR-transferase**
* **Classic A-B type exotoxin**
* _A subunit_ (active) ⇒ transfers ADP-ribose from NAD to G protein that regulates adenylate cyclase activity
* **Host cell cannot turn off cAMP production**
* **Cell loses control of ion flow and cellular processes**
* _B subunit_ (binding) ⇒ mediate attachment to carb moieties on host cell surface
* Translocates A subunit across the membrane
* Biological effects depend on cell type
* **Histamine sensitization**
* **Lymphocytosis**
* **↑ Mucus production**
* **Insulin secretion ⇒** hypoglycemia
* **Alteration of immune effector cell functions**
* **↓ Oxidative killing capacity**
33
B. pertussis
Pathogenesis
Organism remains in the URT.
Exotoxins move to LRT and throughout body.
34
Pertussis
Clinical Stages
Colonization of ciliated bronchial epithelium ⇒ **incubation for 7-10 days.**
Immobilization and destruction of epithelial cells.
No tissue invasion or dissemination.
_3 stages of disease:_
1. **Catarrhal stage** (1-2 weeks)
* Malaise, fever, sneezing, anorexia
* Profuse and mucoid rhinorrhea
* _Highly communicable_ with large # of organisms in NP and mucoid secretions
2. **Paroxysmal coughing stage** (2-4 weeks)
* 40-50 coughing episodes per day
* Characteristic inspiratory whoop
* Air drawn through narrowed glottis
* Coughing and breathing disruption ⇒ child turns red or blue
* May result in vomiting or choking on respiratory secretions
* Lymphocytosis w/ 70-80% lymphocytes
3. **Convalescent stage** (3-4 weeks)
* Gradual fade of sx
* At risk for secondary complications
35
Pertussis
Complications
Usually limited to the URT.
_Infrequent complications may include:_
* **Bronchopneumonia**
* Either due to B. pertussis or superinfection
* Staph, S. pneumoniae, H. influenzae
* **Acute encephalopathy**
* See convulsions resulting in death or permanent brain damage
36
Pertussis
Adolescent/Adult Disease
* Mild URT infection
* Cough with vomiting
* **Cough persisting \> 2 weeks**
* Whooping variable
* Source of transmission to non or partially immune infants
37
Pertussis
Lab Diagnosis
* NP swab ⇒ must be dacron or calcium alginate
* **Culture during first 4 weeks of infection**
* Grown on charcoal blood agar (Bordet-Gengou medium)
* Takes 3-7 days for final ID
* **PCR in conjunction with culture** ⇒ becoming the standard
* **Direct Immunofluorescent Assay** ⇒ can be performed on swab specimens
* Sensitivity ~ 50%
* Most useful in ID'ing B. pertussis after culture
* Mainly a clinical dx
38
Pertussis
Treatment
* **Macrolides**
* _Effective during catarrhal phase_
* Preventative therapy
* **Erythromycin** ⇒ drug of choice
* **Supportive therapy**
* Only option once paroxysmal phase reached
* Manage paroxysms, apnea, cyanosis, feeding difficulties
39
Pertussis
Immunity
* **Infection or immunization ⇒ protective immunity**
* _Not life-long_
* sIgA prevent attachment
* Ab's that neutralize PT
* Repeat infections are mild
40
Pertussis
Prevention
* _1st gen_ ⇒ **heat-killed prep of whole organism**
* **Post-vaccinal encephalopathies**
* _2nd gen_ ⇒ **acellular vaccine**
* **Pertussis toxoid** + 2-4 other virulence factors
* Diphtheria, Tetanus, acellular pertussis series (**DTaP**)
* 5 doses ⇒ 2, 4, 6 m/o, 6 yr, 11-12 y/o
* Booster during pregnancy @ 27-36 weeks ⇒ passive protection of infant
* ↓ Neurologic complications
* **Cocooning infant** ⇒ boost everyone in close proximity
41
DTap vs Tdap
**DTaP** ⇒ initial and boosters in children
**Tdap** ⇒ boosters in adolescents and pregnant women
42
Pertussis
Re-emergence
* Immunity wanes over time
* Adolescent/adults susceptible
* Reservoir for transmission to infants
* Many cases in infants prior to or because of delayed immunization
* Need to boost mother otherwise no maternal passive immunity
* Vaccine boosters recommended q10 years
43
Corynebacterium
Overview
* **C. diphtheriae**
* Pathogenic & highly toxigenic
* Causes **Diphtheria**
* Vaccine preventable illness
* Effects due to exotoxin
* **Diphtheroids** ⇒ commensal organisms
* C. ulcerans, C. xerosis, C. pseudodiphtericum
* Normal flora of pharynx, nasopharynx, distal urethra, and skin
44
C. diphtheriae
Characteristics
* **Small, pleomorphic club-shaped gram ⊕ rods**
* "Chinese letter" or palisade arrangements
* Non-spore forming
* **Aerobic**
* **± metachromatic granules** ⇒ stains bluish-purple w/ methylene blue
* Grown on **Tinsdale agar**
* Contains **potassium tellurite**
* ⊗ normal flora
* Reduced by C. diphtheriae to produce brown to black colonies
45
C. diphtheriae
Transmission & Epidemiology
* **Respiratory droplet or direct skin contact**
* Only reservoir in humans
* **Maintained in population by asymptomatic carriage in oropharynx or skin of immune individual**
* Outbreaks in populations w/o immunization programs
* Ex. End of Soviet Russia
46
Diphtheria Toxin
| (DT)
**Most important virulence factor of C. diphtheriae**
**⊗ Protein synthesis ⇒ Cytotoxic effect**
_A-B type structure_
* _B subunit_ ⇒ **binds** **heparin binding EGF-receptor**
* Receptor mediated endocytosis
* Facilitates translocation of A subunit into cytosol
* Highly expressed on cardiac and neural tissue
* _A subunit_ ⇒ **ADP-ribosylation of elongation factor-2 (EF-2)**
* Required for translocation of polypeptidyl-tRNA from A site during protein synthesis
47
Diphtheria Toxin
Regulation
* ***tox* gene** codes for DT
* Carried by lysogenic or temperate **β-phage**
* Lysogen required for disease
* **Lysogenic conversion** ⇒ non-toxigenic to toxigenic upon phage infection
* **tox gene regulated by DtxR repressor + iron**
* Chromosomally encoded by C. diphtheriae
* Low iron ⇒ tox gene de-repressed ⇒ DT made
* Iron critical for virulence
48
C. diphtheriae
Pathogenesis
49
C. diphtheriae
Clinical Manifestations
* **Malaise, sore throat, fever**
* **Gray-white pseudomembrane** on tonsils, uvula, soft palate, or pharyngeal wall
* Bleeds when scraped
* May obstruct breathing & detach in young children ⇒ ± suffocation
* Cervical lymphadenitis and edema ⇒ **"bull-neck"**
* DT disseminates w/ varied sx
* Cardiac ⇒ **arryhthmias, myocarditis, CHF**
* Neuro ⇒ **neuritis, diaphragm paralysis, coma**
50
Cutaneous Diphtheria
**Infection of the skin w/ C. diphtheriae**
Chronic skin ulcer with a dirty-gray membranous base
51
Diphtheroid
Infection
**Non-toxigenic strains cause non-diphtherial disease.**
Mild pharyngitis
Endocarditis
Septicemia
Abscess
52
C. diphtheriae
Lab Diagnosis
* Swab pharynx
* Culture on **Tinsdale agar w/ potassium tellurite** ⇒ grey/black colonies
* Demonstrate toxin activity ⇒ **Elek test or PCR**
* Immunodiffusion and tissue culture assays
* No rapid tests ⇒ initial clinical dx and treatment
53
Diphtheria
Treatment
* _Eliminate toxin producing bacteria_
* **PCN or erythromycin**
* _Neutralize toxin_
* Passive admin of **equine anti-toxin**
* Heterologous anti-serum ⇒ risk of serum sickness (type III hypersensitivity)
54
C. diphtheriae
Immunity
Largely dependent on presence of Ab that neutralize DT
55
Diphtheria
Prevention
Active immunization with **diphtheria toxoid**
* Prevents disease
* Part of DPT series @ 2, 4, and 6 m/o
* Diphteria, pertussis, tetanus (DTaP)
* Boosters
* Between 4-6 y/o
* Before entering school
56
Childhood Vaccine Schedule
24 immunizations in the first 18 months of life
