Infection/Immunology Flashcards
What proportion of cases of meningitis are viral?
What is the incidence of meningococcaemia?
2/3rds
Incidence meningococcaemia 0.7-1.4 in 100,000
How is meningococcus transmitted?
Large % have nasal/resp tract carriage
Transmitted via aerosol / nasopharyngeal secretion
What are the main virulence factors of meningococcus?
Polysaccharide capsule
Lipo-oligosachharide endotoxin (mediates invasion)
Immunoglobulin A1 protease (help org survive intracell)
At what ages are the Men C vaccine given?
3m, 4m + 1yr
Describe the physiology behind meningococcus effect on meninges/brain
Inflamm mediators + leucocytes → endothelial damage
→ Cerebral oedema
→ Raised ICP
→ Reduced cerebral blood flow
What are the main causative organisms of meningitis in:
Neonates (3)
1m-6yrs (3)
6yrs+ (2)
Neonates: GrpB Strep, E.Coli, Listeria
1m-6yrs: N.Meningitidis, S.pneumoniae, H.influenzae
6yrs+: N.Meningitidis, S.Pneumoniae
List some possible symptoms of bacterial meningitis in neonates (8)
NB more non-specific
Hyperthermia
Vomiting
Seizures
Bulging fontanelle
Irritability
Altered sleeping/eating
High pitched cry
Quiet child at rest but cries when moved/comforted
List some possible symptoms of meningitis in 3m-2yrs (5)
+ in >2-3yrs
NB more bact-associated
Vomiting
Fever
Irritability
Lethargy
Change in behaviour
In >2-3y/o: above + meningism (headache, stiff neck, photophobia)
What % of meningococcal meningitis get the rash?
Describe the rash (site + form)
Common: 50-80%
Axilla/flank/wrists/ankles
Non-blanching petechial rash (due to vasculitis)
Irregular in size
Necrotic centre
What other conditions to meningitis may exhibit neck stiffness? (2)
Tonsillitis
Cervical lymphadenopathy
What viruses may cause meningitis? (4)
Enteroviruses
Adenoviruses
Mumps
Epstein-Barr
What signs may be seen O/E in meningitis? (4)
Petechial rash (meningococcal)
Opisthotonus (arched back: raised ICP)
+ve Brudzinski (neck flexion supine → knee/hip flexion)
+ve Kernig (hip flex /knee extension supine → back pain)
What are the 4 element features of septicaemia?
Capillary leak: severe hypovol
Coagulopathy: bleed tendency + thrombosis in microvasc
Metabolic derangement: acidosis + hypokal/cal/mag/phos
Myocardial failure: direct damage from inflamm meds (func impaired even after circ vol/metab abns restored)
What signs may be seen on cardiac examination with septicaemia? (3)
Raised CVP
Hepatomegaly
Gallop rhythm
What are the features of meningococcal septicaemia? (10)
Fever
Vomiting
Headache
Rash (erythematous → petech/purpuric)
Hypotension
Tachycardia/pnoea
Cool extremities
Initially normal consciousness level
Myalgia
Abdo pain
What is the difference b/wn meningococcal septicaemia + meningococcal meningitis?
Septicaemia: pts present with shock
Meningitis: pts mainly present with raised ICP
List some DDx for meningococcal septicaemia (6)
Sepsis Febrile convulsions Measles/mumps ITP HSP Reye's syndrome (rapid encephalopathy from aspirin)
What is the immediate management of any child with a fever + purpuric rash?
Immediate IM benzylpenicillin + urgent transfer to hospital
What is the commonest pathogenic cause of sepsis in children?
Meningococcus
What Ix should be done if suspect meningococcal septicaemia? (11)
FBC Coag screen U+Es LFTs Blood gases Blood glucose
LP Cultures: urine/blood/throat/stool Rapid antigen test (for meningitis orgs) CXR (if suspect TB) Consider CT/MRI + EEG
Describe the management of meningococcal septicaemia (6)
Empirical broad spec Abx (depends on likely pathogen - usually 3rd gen cephalo like ceftriaxone/cefotaxime)
CVP
Catheterisation
Mechanical ventilation
Iotropic support (for myocardial contractility)
FFP + Platelets → correct any DIC (widespread microvasc thrombosis)
As well as Abx, what other drug must be given in meningococcal septicaemia for neonates?
Abx + Dexamethasone (reduce risk of long-term complications e.g. deafness)
What prophylaxis is given for household contacts of meningococcemia?
Rifampicin (eradicate nasopharyngeal carriage)
Men C vaccine
What is the mortality rate of meningococcaemia?
What is the incidence of serious complications?
15-20% neonates
5% risk in childen older than this
10-15% will have focal neuro sequelae
What are the possible complications on the nervous system of meningococcaemia? (9)
Hearing loss
Visual field defects
Facial palsy
Local vasculitis → CN palsy/ other focal lesion
Hemiparesis
Hydrocephalus Subdural effusion (pneumococcal + HiB)
Epilepsy (local cerebral infarct → multi/focal seizures)
Cerebral abscess
What are the other (not CNS) complications of meningococcaemia (6)
Bacterial endocarditis
Pericarditis
DIC
Thrombocytopenia
Septic arthritis
Gangrene
What may be the underlying cause in pts with recurrent meningococcaemia?
Underlying immune deficits
30% recurrent meningococcaemia have complement defc
What are the poss causative organisms for neonatal early onset sepsis (4) + neonatal late onset sepsis (7)
Early (from birth canal):
GrpB Strep / E.Coli / Listeria / H.Influenzae
Late (from environment): Staph epidermidis Staph aureus E.Coli / Enterococci / Klebsiella / Pseudomonas Candida
What are the 2 main ‘at risk’ groups for septicaemia + common associated pathogens?
Immunodeficient: pneumococcus
Chronic resp illness: pseudomonas
Describe the physiology behind Shock
= Inadequate substrate/oxygen delivery
→ anaerobic → lactic acid accum
→ Cannot maintain homeostasis → disrupt ion pumps
→ intracellular Na influx / K efflux
→ Cells swell / memb breakdown / cell death
→ Multiorgan failure
What are the 3 main features in which you should assume shock?
Prolonged CRT
Tachycardia
Cool extremities
What are some early (compensated) features of shock (8)
Tachycardia Tachypnoea CRT > 2s Core-peripheral temp gap >4 degrees Pale/cold/mottled skin
Sunken eyes/fontanelle
Reduced skin turgor
Reduced urine output
What is the physiological mechanisms behind early/compensated shock
BP maintained by increased HR/RR
Blood diversion from non-essentials e.g. skin
What are some late (decompensated) features of shock (6)
Acidotic breathing (Kussmaul)
Bradycardia
Blue peripheries
Hypotensive
Confusion/reduced consciousness
Anuria
What empirical Abx for sepsis are given in neonates?
+ in older infants / older children?
Neonates: ampicillin + gentamicin/3rd gen cephalo
Older: 3rd gen cephalo
Outline the management of shock (9)
BLS
Abx
High-flow O2
Volume replacement (20ml/kg)
Intubation/ventilation
(if still shocked after 2x VR - even if still alert)
Correction of acidosis
Correction of elec abns
Correct coagulopathy → FFP
Correct anaemia → blood
How is management of fluid resuscitation different depending on whether responsive to initial volume replacement
Responsive: monitor/reassess for further shock/pulm oedema
Unresponsive: further VR (may have 2x bolus) + poss ionotropic support + poss adrenaline
Describe Type 1 Hypersensitivity reaction: initial + subsequent
Initial: allergen → antigen-presenting cell → Thelper
→ B cells (with IgE-bound)
Thelper cells produce cytokines → B cells prolif
→ plasma cells (IgE producing)
IgE → mast cells (now sensitised)
Subsequent: allergen → mast cell IgE
→ Inflamm mediator release
(preformed e.g. histamine + arachidonic acid derived)
→ Vasodilation / SM contraction
→ Small vessel permeability
→ Mucus secretion
What Ix may be done into allergies? (4)
Detailed clinical Hx
Hypersensitivity marker bloods
Patch testing (cutaneous allergens)
Stimulus introduced in controlled conditions
What other condition is assoc w. eczema in young infants?
What conditions assoc w. allergic rhino-conjunctivitis? (4)
Link b/wn eczema + food allergy (esp egg)
Eczema, sinusitis, adenoidal hypertrophy, asthma
Define effects of mild/moderate/severe insect sting hypersensitivity
Mild → local swelling
Moderate → generalised urticaria
Severe → systemic symps with wheeze/shock
What types/drugs are commoner for allergic reaction? (6)
Antibiotics (penicillins/cephalosporins) Anaesthetics (lidocaine) Analgesics (aspirin, NSAIDs) Dextran (anticoag) Opiates Radiocontrast media
What are the short-term risks in HIV infection (2)
What are the long-term risks (6)
Opportunistic infections
Pancytopenia (thrombi/anaemia/neutropenia)
Non-compliance Transmission Failure to thrive Cancers (Kaposi's sarcoma, Non-Hodgkins) Neuropathy/myelopathy HIV encephalopathy
What is EBV infection characterised by? (4)
1-2wks H/o malaise/fatigue (persisting fatigue)
Pharyngitis
Generalised lymphadenopathy
Hepatosplenomegaly
List the possible symptoms that may be seen in EBV/Glandular fever (6)
Fever (>90%) Sore throat Headache Nausea Myalgia Abdo pain
List some possible complications of EBV infection (10)
Harry Tries Justifying His Stupid ‘Necessities’ + Unrealistic Costly Recreational Plans
Hepatitis (90%) Thrombocytopenia (mild) (50%) Jaundice (5%) Haemolytic anaemia Splenic rupture (req splenectomy) Neuro complications (coma/meningitis/enceph/CN palsy) Upper airway obstrn Chronic fatigue syndrome Reye syndrome Peri/myocarditis
What is Kawasaki disease
What age group does it affect?
Rare type vasculitis of medium-sized blood vessels
Affects <5yrs
How may Kawasaki disease present?
What are the Dx criteria? (6)
Severe fever unresponsive to meds + viral-like symps
Temp ≥38 for >5d plus at least 2 of:
Rash
Cervical lymphadenopathy
Conjunctivitis (bilateral)
Oral/throat changes (cracked lips/strawberry tongue)
Arm/leg skin changes (swelling/red/peeling)
How long spent in acute/sub-acute/convalescent phase of Kawasaki disease?
Acute (Weeks 1-2)
Sub-acute (Weeks 3-4) (less severe symps)
Convalascent (weeks 4-6) (lethargy persists)
List the symptoms that may be seen in the sub-acute phase of Kawasaki disease (8)
Lethargy Headache Joint pain Peeling skin Abdo pain Jaundice D+V Pyuria
In what phase of Kawasaki disease are complications most likely to happen?
What is the main concerning complication involved with mortality?
What is the mortality rate of Kawasaki disease?
Sub-acute phase:
Coronary aneurysms likely to develop (in 1/3rd pts)
→ MI / Sudden death
Mortality 1-2%
What Ix can be done into Kawasaki disease? (4)
How is it Dx?
CRP/ESR (raised)
WCC (raised)
Platelets (raised - in 2nd wk)
ECHO (for aneurysm)
Clinical Dx
Describe the management of Kawasaki disease (4)
Prompt IVIG (+ infliximab/steroids/ciclosporin if persistent)
Aspirin: high dose until fever/inflamm markers normal + low-dose until normal ECHO
Antiplatelets (if platelets high)
Long term warfarin (if large aneurysm)
List some possible non-deliberate causes of immunosuppression (5)
Malnutrition
Ageing
Certain cancers (leukaemia/lymphoma/multi-myeloma)
AIDS
Drug side effect (treating other condition)
List/catagorise the different causes of immunodeficiency (1+7)
Primary (uncommon): inherited / autosomal recessive
Secondary: Intercurrent viral/bacterial HIV Malignancy Malnutrition Immunosuppressants Splenectomy Nephrotic syndrome
What is immunodeficiency characterised by?
SPUR infections:
Serious / Persistent / Unusual / Recurrent
List some diff T cell defect conditions (6)
Severe Combined Immunodefc (SCID) (inheritable) HIV (progressive defc) DiGeorge syndrome (absent thymus) Duncan syndrome (abnormal EBV response) Wiskott-Aldrich (triad w. thrombocytopenia/eczema) Ataxia Telangiectasia (DNA repair defect)
List some diff B cell defect conditions (4)
Selective IgA defc (commonest)
X-linked agammglobulinaemia
(abnorm tyrosine kinase - for B cell maturation)
Common Variable Immunodefc (CVID) - B cell defc
(high risk autoimmune + malignancy)
Hyper IgM syndrome
(B cells make IgM but cannot switch it →IgG/A)
How do T cell defects present? (5)
In 1st 3m Severe/unusual viral/fungals Failure to thrive Severe bronch/diarrhoea/oral thrush PCP
How do B cell defects present? (4)
In 1st 2yrs (beyond infancy due to passive immunity)
Failure to thrive
Severe bacterial infections (ear/sinus/skin/pulm)
Complications of recur rents (bronchiectasis/hearing loss)
How do neutrophil defects present (5)
Recurrent bacterial infections Abscesses Poor wound healing Invasive fungals e.g. aspergilliosis Granulomas (from chronic inflamm)
Give an example of neutrophil defect
Chronic granulomatous disease
X-linked recessive phagocytosis defect
How do leucocyte function defects present? (4)
Delayed umbilical cord separation
Delayed wound healing
Chronic skin ulcers
Deep seating infections
Give an example of leucocyte function defect
Leucocyte Adhesion Defect (LAD)
Inability for neutrophils to migrate to inf/inflamm site
How do complement defects present? (2)
Recurrent bacterial + meningococcal infections
SLE-like illness
Give 3 examples of complement defect conditions
Early complement component defc
Terminal complement component defc
Mannose-binding lectin (MBL) defc
What are the 5 options for prevention/treating infections in immunodefc? (PIGS in Bs)
Antimicrobial prophylaxis:
T-cell/neutrophil → co-trimox (PCP) / antifungals
B-cell → Abx (azithromycin)
Ig replacement
Gene therapy (certain types SCID)
Screen for end-organ disease
Bone marrow transplant
What pathogens may cause typhoid fever? (2)
What is the route of transmission
Salmonella thyphi
Parathyphi infection
Via contaminated food/water
What are the clinical features of typhoid fever? (10)
Worsening fever Malaise/myalgia Headache Cough Bradycardia
Abdo pain
GI symps (2nd wk)
Anorexia
Splenomegaly
Rose spots**
What are the poss complications of typhoid fever? (4)
GI perforation
Myocarditis
Nephritis
Hepatitis
What age children are affected worse by malaria?
What % of child deaths?
6m-5yrs
Where endemic = 10% all child deaths
What are the clinical features of malaria
Fever Thrombocytopenia Anaemia Jaundice D+V Flu-like symptoms
What happens in cerebral malaria?
What are the main features (2)
Rapid encephalopathy (occurs in 20-50% pts) from parasites adhering to cerebral microvasc (→ ischaemia/blockage)
Raised ICP
Seizures
