2. Epidemiology, Presentation & Diagnosis Flashcards
1
Q
ID: Environment
A
- Climate
- Geography
- Healthcare systems
- Exposure
- Social
2
Q
ID: Host
A
- Symptoms
- Immunity/Susceptibility
- Risk behaviour
- Lifestyle
3
Q
ID: Pathogen
A
- Virulence
4
Q
Infections could be:
A
- Endogenous - arise from within the body e.g. bacteria
- Exogenous - superficial layers of the skin
- Subclinical - asymptomatic
- Clinical - disease
- Caused by flora, colonising organisms, or exogenous organisms
5
Q
Types of skin infections:
A
- Cellulitis - affects dermis & subcutaneous tissues (deeper layers)
- Erysipelas - superficial layers of the skin
- Impetigo - school sores
- Shingles / Chicken pox - caused by the same virus
- Necrotising faciiitis
- Carbuncles (boils) - caused by S. aureus
- Lymphangitis (associated with cellulitis)
6
Q
Cellulitis: How does bacteria cause illness?
A
- Bacteria colonise skin
- Bacterial toxins (cytolysins) damage epithelial cells
- Damaged epithelial cells release cytokines (e.g. IL-1, TNF-a, IL-8 which contributes to neutrophil chemotaxis)
+ Cytokines are produced by injured & healthy cells (via stimulation of TLRs)
+ IL-1 & TNF-a instruct capillary endothelial cells to express cellular adhesion molecules (e.g. selectins, CAMs) - Skin macrophages & dendritic cells follow chemical gradient to the site of infection - also release cytokines
- Selectins interact with carbohydrates on neutrophils causing them to slow, roll & tether to epithelium - diapedesis
- Tethered neutrophils are pulled between the epithelium (vie PECAM interactions) & migrate to the site of infection - chemotaxis
- PAMPs (e.g. peptidoglycan lipotechoic acid) bind to PRRs (e.g. toll-like receptors) which activate innate immunity
7
Q
Complement immune response
A
- Lectin pathway: Bacterial carbohydrates binds to proteins
- Alternative pathways: Complement spontaneously starts to form on cell surfaces
- Classical pathways: Antibody, immunoglobin binds to bacterial antigen
- Once triggered a number of proteins combine to for C3 convertase which cleaves C3 into C3a & C3b
+ C3b is an opsonin - binds to bacteria & enhances recognition & phagocytosis - Some C3b binds back to the C3 convertase to form C5 convertase which cleaves C4 in C5a & C5b
+ C5b binds with C6 to C9 to form the membrane attach complex (MAC) which lyses bacteria (gram negative) - C3a & C5a are anaphylatoxins - increase vascular permeability
+ C5a is also a chemotactic protein
8
Q
End result of bacterial infections (Cellulitis)
A
- Increased vascular permeability in the skin leads to erytherma
- Changes to larger vessels & lymphatic vessels leads to swelling
- Purulent materials contain neutrophils & other phagocytes, dead cells, viable bacteria, dead bacteria, cell debris & extracellular protein
- Cytokines, cellular debris & bacterial degradation products stimulate nerves to cause pain
9
Q
Causes of cellulitis
A
- Streptococcus pyrogenes
- Staphylococcus aureus
- Other bacteria
10
Q
Causes of boils/furuncles:
A
- S. aureus
11
Q
Causes of other skin infections:
A
- Fungi
- Viruses
12
Q
Streptococcus pyrogenes:
A
- Gram positive cocci
- Colonises 10-15% of oropharynx
- Also causes: Pharyngitis, Skin & soft tissue infections
- Bone & joint infections
- Rheumatic fever
13
Q
How does S. pyrogenes avoid the immune system & cause disease”
A
- Various toxins (streptolysins) damage cells such as neutrophils & platelets
- DNAses digest DNA to avoid being trapped in neutrophil extracellular traps
- Streptokinase activates plasminogen into plasmin which digests fibrin
- Adhesins which bind to host tissues (MSCRAMMs = microbial surface components recognising adhesive matrix molecules)
- Hyaluronic acid capsule prevents opsonisation & phagocytosis
- C5a peptidase degrades C5a reducing chemotaxis
- M proteins (another MSCRAMM) binds factor H, which degrades complement
+ M proteins also interfere with C3 binding to C3b receptor on phagocyte cell
+ There are different types of M proteins & often a particular M protein is associated with a particular disease
14
Q
Diagnosis of bacterial illness (cellulitis)
A
- Clinical (look at skin) + Blood tests looking for antibodies/cytokines
- Lab swabs of purulent material
- If admitted to hospital, blood cultures should also be taken
+ Very sick individuals should be tested for sepsis (e.g renal failure)
15
Q
Treatments for cellulitis
A
- Antimicrobial drugs that are primarily directed at S. pyrogenes & S. aureus
- Analgesia
- Lifestyle changes such as supportive care (maintain “normla” physiology), rest & elevation
16
Q
Treatment of cellulitis - Penicillin
A
- Penicillin binds to transpeptidase, preventing cross-linking
- Inhibition of transpeptidase impairs repair of cell wall & leads to release of autolysis that digest the cell wall
- Bacterium dies
Penicillins:
- Peptidoglycan is the main component of bacterial cell wall
+ N-acetylmuramic acid (NAM)
+ N-acetylglucosamine (NAG)
+ Glycans have peptide chains – alanine, glutamine, lysine & alanine
+ Cross-linked terminal peptides (lysine to terminal alanine) - Transpeptidase (penicillin binding protein – PBP) forms bonds between tetrapeptide chains
17
Q
Penicillins - B lactam antibiotics
A
- Structure: B-lactam ring + Thiazolidine ring + Side chain
- Includes all penicillin derivatives, cephalosporins, carbapenems & the monobactam
- All S. pyrogens are susceptible to penicillin, but only 10% of S. aureus are
18
Q
Cellulitis - Risk factors
A
~1500 cases at Auckland Hospital
Risk factors for cellulitis include:
- Prior cellulitis (24%)
- Diabetes (21%)
- Morbid obesity (18%)
- Chronic venous insufficiency (12%)
- Heart failure (12%)
- Prior DVT (4%)
- Peripheral vascular disease (4%)
- Immunosuppressed (3%)
- Maori & Pacific people are at increased risk of skin infection in NZ
19
Q
Endocarditis
A
- Inflammation on heart valves or other cardiac structure (e.g. ventricular septal defect)
- Almost always caused by bacterial infection
- Clumps on heart valves will grow a ton of bacteria
20
Q
Endocarditis & heart function
A
- As myocardium contracts, blood flows through the aortic valve into the aorta
- As the myocardium relaxes, the aortic valve closes & prevents blood falling back into the left ventricle
- If the aortic valve is leaking, as the myocardium relaxes, blood can flow back into the ventricle – this blood flow (regurgitation) is turbulent
- The shearing forces of turbulent blood flow, over long time periods, can damage endothelial cells on the surface of the connective tissue (valve) and can expose the connective tissue matrix
- A wide range of bacteria (staphylococci & streptococci) have surface molecules that recognise & bind to exposed connective tissue
- Bacteria in the blood stream that bind to exposed connective tissue due to turbulent blood flow caused by a leaking heart valve can form a mass – a vegetation = ENDOCARDITIS
- Endocarditis can occur on any heart valve, septal defect, pacemaker wire…
21
Q
Common risk factors for endocarditis
A
- Valve damage: \+ Rheumatic fever \+ Mitral valve prolapse \+ Bicuspid aortic valve \+ Congenital heart disease - Old age - Prosthetic valve - Other cardiac device - IV drug use - Recent cardiac surgery - Central venous catheters
22
Q
Clinical features of endocarditis
A
Systemic:
- Fever (80%)
- Chills (60%)
- Aches/pain (20%)
- Weight loss
- Sweating
- Lethargy
Valve:
- Leaking
- Cardiac abscess
- Need for surgery (30%)
Embolic:
- Infection at another site
- Stroke
- Leg/gut artery occlusion
Vasculitis:
- Glomerulonephritis (20%)
- Splinter haemorrhages (30%)
- Other (10%)
23
Q
Diagnosis of endocarditis
A
- Persistent bacteraemia with usual organism
- Ultrasound of heart valves to visualise vegetations
- Presence of other phenomena
24
Q
Treatment of endocarditis
A
- Sterilise the valve with surgery of antibiotics
- Usual treatment with bactericidal antibiotic (penicillin)
- 10 - 30% mortality
