Lecture 17-Bacterial infection-pneumococcal disease

Question 1

how many serotypes identified so far? what are they based on? challenge for treatment

Answer 1

> 90; based on the structural difference in capsule; vaccines that cover all these different types is a challenge

Question 2

what is pneumococcal disease? (PD)

Answer 2

bacterial infection of URT causing pneumonia, meningitis, sepsis and otitis media

Question 3

where is PD a major burden?

Answer 3

in areas where vaccine has not been introduced e.g. sub saharan africa, india, china

Question 4

reasons for child survival gap between ethiopia and germany?

Answer 4

infections left untreated or inadequate prevention/treatment (vaccine)

Question 5

two types of PD?

Answer 5

non-invasive- e.g. otitis media, pneumonia

invasive e.g. meningitis, sepsis

Question 6

correlation between disease severity and prevalence

Answer 6

as disease severity increases, prevalence decreases e.g. meningitis most severe but least prevalent compared to otitis media

Question 7

indigenous population rates

Answer 7

high rates- perhaps genetic factors?

Question 8

age risk for PD

Answer 8

extremes of age
<5 years
>65 yrs

Question 9

populations at risk

Answer 9

children in developing countries, indigenous population of developed countries

Question 10

how does chronic illness affect your risk of PD?

Answer 10

chronic illness (HIV) or the immunocompromised increases your risk

Question 11

what is the greatest risk factor for getting PD?

Answer 11

recent acquisition of a new virulent strain (when immunocompromised or in a high risk population)–>strain disseminates and cause disease

Question 12

what type of organism is streptococcus pneumoniae?

Answer 12

ubiquitous organism, even considered a commensal

Question 13

nasopharyngeal colonisation

Answer 13

prerequisite for disease

• airborne droplets enter nasopharynx, carriage
• local spread to ear (otitis media) or sinus (sinusitis)
• aspiration to alveoli (pneumonia)

Question 14

what do you want to prevent in disease pathway?

Answer 14

prevent carriage to prevent disease dissemination and spread to someone else

Question 15

colonisation during early life factors

Answer 15

first days to weeks- asymptomatic

- within 3 years, 50% people colonised, earlier in some settings

Question 16

colonisation during adult life

Answer 16

relatively stable carriage in older children/adults

Question 17

streptococcus pneumoniae death rate

Answer 17

11% of deaths in children under 5 years of age worlwide

Question 18

2 main pneumococcal virulence factors

Answer 18

polysaccharide capsule

pneumolysin

Question 19

polysaccharide capsule function

Answer 19

inhibits phagocytic clearance and reduce antibiotic exposure (defence mechanisms that enable its survival)

Question 20

pneumolysin function

Answer 20

pore forming cytotoxin, impair respiratory burst (impair neutrophil function)

Question 21

other pneumococcal virulence factors

Answer 21

PspC-pneumococcal surface protein C and other proteins

Question 22

techniques of pneumococcal capsule

Answer 22

level of capsule differs during carriage and invasion
- thick- be away from immune system and protected
-thin- when invading
immune protection based on capsule-specific Ab (IgM, IgG)

Question 23

what is the basis of current vaccine formulations ?

Answer 23

pneumococcal capsule

Question 24

host response to pneumococcal infection

Answer 24

• pneumococcus releases toxins to promote growth and survival, spreads into tissues
• Ab deposited, binds to bacteria, facilitates removal through complement mediated phagocytosis

Question 25

opsonophagocytosis

Answer 25

clearance by complement component and phagocytosis by neutrophils

Question 26

serotype-specific immunity

Answer 26

host response to pneumococcal infection | -since colonisation is immunising (memory B cells, CD4T cells)

Question 27

IL-17A

Answer 27

protective against colonisation; helps facilitate removal of bacteria

Question 28

how is S.pneumoniae detected?

Answer 28

invasive disease detected from sterile site (blood, CSF);; other sites (sputum, urine)- gram stain - capsule swelling by specific antibody-shows what serotype is causing infection

Question 29

3 types of pneumonia

Answer 29

- community acquired acute pneumonia (CAP) e.g. strep pneumoniae, H.influenza - community acquired atypical pneumonia e.g. viruses (A and B), chlamydia - hospital acquired pneumonia e.g. pseudomonas

Question 30

what is bacterial pneumonia?

Answer 30

severe CAP- most common cuase of death from infections in developed countries (low fatality, but most common cuase)

Question 31

what does bacterial pneumonia occur in association with?

Answer 31

other causes of infection- viral infection (e.g. influenza)- co infection

Question 32

what happens in bacterial pneumonia?

Answer 32

inflammation of lungs accompanied by fluid-filled alveoli and bronchioles- reduce ability to exchange gases and respiratory failure -described by affected region or organism causing disease e.g. lobar or broncho

Question 33

is pneumonia invasive or non-invasive?

Answer 33

non-invasive

Question 34

is meningitis invasive or non-invasive?

Answer 34

invasive

Question 35

is sepsis invasive or non-invasive?

Answer 35

invasive

Question 36

is otitis media invasive or non-invasive?

Answer 36

non-invasive

Question 37

what is the pathogenesis of pneumonia?

Answer 37

- pneumococcus invades airspace-->interactions between bug and receptors (TLRs on alveolar macrophages) - response-->cytokine production (in most conditions enough to clear infection) - chronic doses-->infiltrates of neutrophils doesnt actually clear infection-->accumulation in air space-->overwhelmed, leakage-->invasion into bloodstream (due to increased permeability)-->severe

Question 38

histopathology of pneumonia

Answer 38

- alveoli filled with inflammatory cells - thickened alveolar wall - congested blood vessels (RBCs) - infected part of lung doesnt function if not treated within time

Question 39

clinical features of pneumonia

Answer 39

onset of severe illness is abrupt (fever, cough, chest pain, chills, productive sputum, dyspnoea)

Question 40

untreated pneumonia-->

Answer 40

acute respiratory failure, septic shock, multi-organ failure

Question 41

two major signs for pneumonia in children

Answer 41

fast breathing | chest in drawing

Question 42

diagnosis of pneumonia

Answer 42

chest x-ray- determine consolidation pleural effusion systemic features (fever)

Question 43

what is meningitis?

Answer 43

infection of the subarachnoid space with meningeal involvement (leptomeningeal inflammation surrounding brain and spinal cord)

Question 44

bacterial causes of meningitis?

Answer 44

most common (S.pneumoniae, N.meningitidis)

Question 45

other infectious causes of meningitis?

Answer 45

viral, fungal, malaria, mycoplasma, rickettsiae

Question 46

non infectious causes of meningitis

Answer 46

malignancy, SLE, lead/mercury poisoning

Question 47

what is the pathogenesis of meningitis?

Answer 47

- translocation across BBB- facilitated by upregulation of receptors on endothelial cells during infection - bacteria multiply-->engage with APCs-->produce cytokines (TNF-alpha, IL-1, IL-6)-->causes inflammation and recruitment of neutrophils-->increase BBB permeability-->intracranial pressure, oedema

Question 48

pathological features of meningitis

Answer 48

inflammatory infiltrate (lymphocytic blood vessels due to increase BBB permeability), oedema

Question 49

clinical signs and symptoms of meningitis

Answer 49

- common- severe headache, high fever, stiff neck, nausea, vomiting - clearer indications- numbness, loss of feelings, light sensitivity, confusion, seizures, rash

Question 50

what is otitis media?

Answer 50

inflammation of the middle ear cavity

Question 51

clinical types of otitis media

Answer 51

many - acute - recurrent - OM with effusion (glue ear) - chronic suppurative OM

Question 52

major consequences of otitis media

Answer 52

hearing loss, developmental problems

Question 53

pathogenesis of otitis media

Answer 53

nasopharyngeal carriage (prerequisite) - accumulation of fluid in eustachian tube (links nasopharynx to middle ear) - leads to otorrhoea (fluid drainage), tympanic membrane perforation, hearing loss

Question 54

acute OM

Answer 54

follows a cold-->leading to active infection and pain | - ear drum can rupture, pus discharge, inflammation, swelling (self-limiting within 2-4 weeks)

Question 55

chronic suppurative OM

Answer 55

initial episode of AOM--> becomes persistent | - usually up to 3 months duration, can spread to brain causing meningitis, hearing loss

Question 56

first line treatment

Answer 56

antibiotics esp penicillin (as we enter resistance, need to find new drugs)

Question 57

two major types of vaccines

Answer 57

``` conjugate vaccines (PCVs) polysaccharide vaccine (PPV) ```

Question 58

conjugate vaccines (PCVs)

Answer 58

in infancy, up to 13 serotypes - take polysaccharide structure from different serotypes, conjugate into protein, makes them immunogenic and long-lasting

Question 59

polysaccharide vaccine (PPV)

Answer 59

older children and adults. 23 serotypes

Question 60

probiotics

Answer 60

alternative strategy to prevent/reduce colonisation

Question 61

what do PCVs produce?

Answer 61

highly functional serotype-specific IgG- protects against IPD, less effective for mucosal disease

Question 62

what impacts efficacy of PCV?

Answer 62

geographic differences in serotype distribution

Question 63

what is serotype replacement?

Answer 63

introduce vaccine --->severe decline in serotype e.g. 7-->rise in non7 type (replacement)-->e.g. 19A increased -->therefore make vaccine for that serotype *vaccine efficacy against IPD

Question 64

19A

Answer 64

most common serotype replacement disease in australia

Question 65

vaccine efficacy of PCV against pneumonia

Answer 65

* non-invasive - correlates of protection less understood - immune response generated by these vaccines may not provide same protection as for invasive

Question 66

nutrition role in disease

Answer 66

undernourished children at increased risk of death - maternal and child nutrition important - zinc, vitamins A/D important (prevent respiratory infections); weakened respiratory muscles, reduce ability to clear infection

Question 67

breastfeeding role in disease

Answer 67

highly protective - exclusive breastfeeding until 6 months until 2 years (developed countries) - developing countries- low rates

Question 68

indoor air pollution role in disease

Answer 68

open stove (high risk), smoke for heating enters child's lungs (increase susceptibility to pneumococcal infection and transmission)