M- Pharyngitis Flashcards
What is the most common cause of URI infections?
What is the most common URI?
Viruses are the most common causes of URI with the common cold (rhinovirus in adults and parainfluenza/coronaviruses in kids) being the most prevalent
What are the potential causes of pharyngitis?
Children under 3 and adults -- viruses Older children (5-15)- GABHS, viruses, mycoplasma pneumonia,
How can you distinguish between virally caused and bacterially caused pharyngitis?
Microbiological tests for GABHS infections.
You cannot tell from clinical grounds alone
What are the 6 main viruses that can cause pharyngitis?
- rhinovirus (children <3 and adults)
- influenza A,B C ( all ages)
- Enteroviruses (older children)
- EBV (older children/young adults)
What are the 3 main bacterial causes of pharyngitis?
- Strep pyogenes (GABHS)
- Mycoplasma pneumonia
- Corynebacterium diptheria
Describe the aerophilicity, mobility, spore forming capability, capsulation and gram stain properties of Corynebacterium diptheriae.
- aerobic
- non-motile
- non-spore forming
- non-capsulated
- gram + bacteria with clubbed ends
What are the special media used to grow C. diptheriae?
- Loeffler’s medium- enriched coagulated serum
2. Potassium tellurite - colonies look grey/black
Where does diphtheria reside?
What is the mode of transmission?
Who is most likely to get pharyngitis from diphtheria?
- cohabitates mucus membrane with saprophytic diptheriods (normal flora)
- transmitted by spread of nasopharyngeal secretions or contact with infected skin exudate and fomites
- elderly, urban poor, immigrants (unimmunized, dwindling immunity)
What are the 3 primary determinants of pathogenesis of diptheriae?
- state of immunity
- site of infection
- virulence/toxigenicity of the organism
What are the local and systemic effects of C. diphteriae infection?
Local:
- pseudomembrane- leathery membrane that covers the tonsils and can extend to involve the pharynx/larynx and bronchi
- bull neck- extensive pseudomembrane, cervical adenopathy, upper airway obstruction
Systemic:
- myocarditis
- neuropathies
Describe the toxin of C. diptheriae.
- lysogenic bacteriophage encoded- “tox” gene
- A-B toxin - B fragment binds to cell surface receptor (pro heparin binding EGF) and the A fragment inhibits protein synthesis by enzymatically transferring ADP-ribose from NAD to EF2
Why can you not remove the pseudomembrane associated with local C. diptheriae infection?
It can cause swelling, bleeding and aspiration
What determines the severity of myocarditis and neuropathy associated with C. diphtheria infection?
The amount of toxin absorbed **not necessarily the number of bacteria present
How are C. diphtheria infections treated?
How are they prevented?
Treatment:
1. anti-toxin - antibody to toxin from horses injected with inactivated diphtheria toxin used for treatment in conjunction with antibiotics
Prevention:
DTaP vaccine- diphtheria toxoid, tetanus toxoid, acellular pertussis components
What are the characteristics of streptococci? Gram staining spores? catalase? motility? oxygen usage?
Gram + cocci in pairs or chains non-spore forming catalase - non-motile facultative anaerobes or microaerophiles
What are the 3 growth patterns of streptococci on sheep agar plates? What is the major organism of each group?
- B-hemolytic- complete clearing indicating lysis of RBCs. S. pyogenes, s. agalactiae, s. bovis,
- alpha hemolytic - partial clearing indicating imcomplete lysis of RBCs and greenish discoloration. s. pneumoniae, s. viridans
- gamma hemolytic- no observable lysis of RBCs. Enterococcus
After you have identified a hemolysis pattern, how can streptococci strains be further categorized?
Which strains are most pathogenic in humans?
By their group specific carbohydrates using Lancefield classification.
It is meant to differentiate b-hemolytic strains, but there are some a/non-hemolytic strains that can be classified with this method.
Serogroups A-H, K-V
Humans are affected by A-D and G
What is the hemolysis pattern of S. bovis?
It is an alpha hemolytic strep that is group D on the lancefield scale
How are GABHS differentiated from other B-hemolytic strep?
Based on sensitivity to bacitracin.
A disk impregnated with bacitracin is placed on a lawn of bacteria and incubated.
If there is a clearing around the disk, the bacteria is sensitive to bacitracin and is GABHS
What is the major virulence factor of GABHS that allows it to be further subdivided?
What are the 3 throat strains?
M proteins are major virulence factors that have a variable region in the exposed amino terminus (over 100 serotypes)
The throat strains are usually M1, M6, M12
What are the 2 ways we are able to classify GABHS by their M proteins?
- humoral immunity - type specific antibodies against certain M proteins
- If non-typeable, CDC can generate DNA sequences of the gene encoding the M protein
What are the 3 major modes of transmission for GABHS?
- Air- respiratory droplets (NOT fomites)
- Food prepared by someone with an open lesion
- Hands (as proven by Semmelweis)
What are the 2 major portals of entry into the human body?
- throat- oropharynx, URT
2. skin
Since no known reservoirs of GABHS exist in nature, _____________ in humans is required for persistence of the organism.
an asymptomatic carrier state
What are the 3 ways GABHS adhere to host tissue?
- M-proteins - bind epithelia and skin keratinocytes
- ECM binding proteins - bind fibronectin, fibrinogen, collagen
- Hyaluronate capsule- binds CD44
What are the 4 ways GABHS avoids host immune response?
- M-protein- antiphagocytic, binds complement regulatory factors
- Hyaluronate capsule -antiphagocytic
- Ig-binding proteins - binds FcR
- C5a peptidase- cleaves complement CFa chemotaxin to prevent neutrophil recruitment
What are the 5 ways GABHS can invade and spread to other tissue?
- SpeB (strep pyrogenic exotoxin B) Protease- degrades host tissue
- Streptolysins- exotoxins that cause hemolysis (S and O are b-hemolytic)
- DNAse
- Streptokinase- degrade clots by activating plasminogen
- hyaluronidase- degrade hyaluronic acid
What are the 2 major ways GABHS cause toxicity?
- Superantigens- activate T cells in the absence of MHC releasing a lot of cytokines
- Streptococcal pyrogenic exotoxins (Spe’s)- lead to scarlet fever and strep toxic shock
How does the host gain immunity to GABHS?
- Humoral immune response (Ab against strep M-proteins, streptolysin O and DNAse)
- Opsonophagocytosis by neutrophils/PMNs
What are the 3 ways Streptococcal diseases are diagnosed? What are pros and cons of each?
1. Culture: \+ = aerobic growth, G+ cocci, B-hemolysis, bacitracin sensitivity - = takes 1 to 2 days 2. Serology \+ = antistreptolysin O, anti-DNAse - = takes a few days 3. Antigen Detection \+ = rapid diagnosis for strep throat - = if it is negative, you have to do a culture or serology
What are the symptoms associated with ACUTE GABHS disease?
- Suppurative (pus-forming) - pharyngitis, skin/soft tissue infection, occasionally deeper tissue involvement
- Toxin-mediated - scarlet fever, Strep TSS
What are the delayed sequelae of GABHS disease?
Throat infections can lead to:
- Rheumatic Fever
- APSGN
Skin infections can lead to:
1. APSGN
GABHS is responsible for the majority of bacteria pharyngitis in what age group? What season?
How does transmission occur?
Children 5-15 in the fall when they return to school and are crowded together Transmission occurs by: 1. respiratory droplets 2. asymptomatic carriers 3. hand to hand contact
What is the incubation period for GABHS?
What are the initial symptoms?
What is the appearance of the oropharynx on physical exam?
When does it usually resolve?
2-4 days after which they get:
- fever
- sore throat with malaise
- headache
- nausea/vomiting in small children
Pharynx is red, edematous, and has petechiae
Tonsils are enlarged and studded with white exudate/plaques
Submandibular lymph nodes are swollen and tender
Symptoms resolve in 3-4 days
How do you differentiate viral pharyngitis from GABHS pharyngitis?
Why does it even matter?
They will present similarly, except viral will have clear runny nose, conjunctivitis and hoarseness.
Run rapid strep test and culture for definitive diagnosis.
You want to treat bacterial strep because you want to avoid the sequelae (APSGN, rheumatic fever) but you would ideally not treat viral because you want to limit antibiotic use to minimize bacterial resistance
What are the 4 drugs used to treat bacterial strep?
When is each justified?
- IV penicillin - if severe with local sequelae
- Benzathine pen G - IM injection
- Oral pen or amoxicillin for 10 days
- macrolides or cephalosporin if pen allergic
What are the 2 major local complications of GABHS infection?
- Peritonsillar sepsis and abscess leading to respiratory compromise
- Cervical adenitis- draining cervical lymph nodes get infected and suppurate to form large abscesses
What is the cause of scarlet fever? Is it the sequelae of a throat infection or skin infection?
Scarlet fever is caused by the release of Spe’s (encoded in bacteriophages and predominantly superantigens) from GABHS.
Symptoms come primarily from pharyngeal disease, but can occur with skin infections too.
What are the clinical manifestations of Scarlet fever?
- diffuse sandpaper rash on upper chest, neck, trunk and extremities (NOT palms, soles, face)
- Pastia’s lines- red lines behind knees, elbows, neck
- Circumoral pallor- pale around the mouth
- Strawberry tongue (white with red papillae)
- raspberry tongue (beefy red tongue)
- desquamation (peeling skin on hands/feet)
What 3 features do all cases of ARF have in common?
- preceding GABHS infection
- incubation 7-21 days
- no GABHS in damaged tissue
What are 3 unique features of rheumatogenic GABHS?
- distinct M serotypes (M6, M14)
- lack of opacity factor
- heavily encapsulated
What are the 2 major theories for the pathogenesis of ARF?
Which is the currently held belief?
- Toxins like Spe, streptolysin O directly cause injury
- Molecular mimicry- Ab formed against M proteins of strep cross react with cardiac and other tissue **currently held belief
What are the major manifestations of Jones criteria?
- Joints (migratory polyarthritis)
- Carditis (pan- heart enlargement, insufficiency)
- Nodules (subcutaneous)
- Erythema marginatum (trunk/proximal extremities, no pain)
- Chorea
What are the 3 clinical minor manifestations of rheumatic fever?
What are the 4 laboratory “minor manifestations”?
Clinical: 1. fever 2. arthralgia 3. previous rheumatic fever Lab: 1. acute phase reactions 2. elevated ESR 3. C-reactive proteins 4. prolonged P-R interval
Using Jones criteria, what must be present to indicate a high probability of presence of rheumatic fever IF previous strep infection is confirmed (cannot rely on prior symptomatic pharyngitis! need serology like ASO titer)?
- 2 major criteria
2. 1 major criteria and 2 minor
Which is more sensitive when testing for ARF, culture or serology?
serology (increased ASO titer)
What age group is most affected by ARF?
5-15 (it is VERY rare under the age of 2)
ARF is preceded clinically by __________________ clinical syndrome but not __________.
pharyngitis but not pyoderma (skin infection)
Describe the risk of repeat attacks of ARF.
What decreases risk?
What increases risk?
They can have repeat attacks, but the risk decreases with time after the first attack,
Risk also has an inverse relationship with age .
Risk is higher in patients with carditis and in patients with high ASO following streptococcal infection
What is the outcome of ARF?
75% of acute attacks subside within 6 wks
If they had carditis- valve damage is common and they are at an increased risk of infective endocarditis
What is treatment for ARF?
- penicillin can prevent development of symptoms and can reduce duration of symptoms
- aspirin can help with inflammatory lesions
How can initial attacks of ARF be prevented?
How long should therapy be given?
Give penicillin within the first 9 days of symptoms of pharyngitis to reduce the risk that it advances to rheumatic fever.
Give treatment for 10 days
How can recurrent attacks of ARF be prevented?
What are the benefits to each strategy?
How long is therapy given?
- daily oral pen V- easier, no hypersensitivity but less effective
- monthly benzathine penicillin IM - more effective but hypersensitivity reaction
Chemoprophylaxis should be given for 5 years or until the age of 25
What is the clinical presentation of someone with APSGN?
5-15 year old with previous GABHS skin infection OR pharyngitis.
Present with:
mild proteinuria and microscopic hematuria to acute renal failure with volume overload and hypertension, edema, encephaly, death.
Urinalysis : proteinuria, RBCs, red cell casts
What are the two main theories for APSGN?
- immune complexes (Ab + strep Ag) form and deposit in the subepithelium of the glomerulus and activate complement
- streptokinase-like enzyme activates plasminogen to make plasmin to promote complement deposition and glomerular hypercellularity
What serological tests are studied for APSGN?
Which is more sensitive?
- elevated ASO in most patients
- antiDNAse B is a more sensitive indicator of prior strep skin infections than ASO
- serum complement is decreased in acute phase (because it is being deposited in the kidney)
What is treatment and usual outcome for someone with APSGN?
Treatment:
- drugs to decrease fluid retention/hypertension
- penicillin to eradicate strep
Outcome:
- usually resolves w/o residual damage
- in adults CAN progress to chronic renal disease but the chance is low
What is the prevention strategy for APSGN?
Benzathine penicillin IM reduces frequency of streptococcal pyoderma (skin infection) in children and can minimize the spread.
