Flashcards in Infection Deck (188):
Ann invasion of hosts tissues by microorganisms
Causing disease by microbial multiplication, toxins or host response
Give some examples of pathogens using different routes of infection
Self - Escherichia coli - Uti
Direct contact - Herpes Simplex Virus - Cold sore
Vector - Plasmodium vivax - malaria
Faeco-oral (food and water) - Clostridium difficile - c diff
Droplet - Influenza - flu
Aerosol - Mycobacterium tuberculosis - TB
Blood - Hepatitis B - hep B
Vertical transmission - cytomegalovirus (placental), Chlamydia trachomatis (delivery)
Differentiate exo and endo toxins
Exo - released by the bacteria usually acting away from the site
Endo - structural components of bacteria
Which types of bacteria are more likely to express endotoxins?
What are the toxins released by c diff
type A create pores in enterocytes
type B are cytotoxic
What pathogen and host factors influence disease severity?
Virulence of pathogen
What are the two broad categories of investigations for infection?
Supportive (e.g. Cxr, fbc)
Specific (e.g. Micorscopy, culture)
What sorts of viruses are effected by alcohol?
Enveloped - disrupts their membrane
Examples of Non enveloped viruses (thus less effected by alcohol)
Paravirus 19 (fifths disease)
Hep A and E
Give some examples of DNA viruses
Counterstain in a gram stain?
Differentiate the types of fungi
Yeast - single cell (e.g. Candida, pneumocystis jiroveci)
Mould - multi cell (e.g. Aspergillus, tinia)
Give 3 examples of protazoa and their disease
Plasmodium - malaria
Giardia lamblia - giardiasis
Trypanosoma cruzi - chagas
Cause of bilharzia
What patient factors influence susceptibility to infection?
Age (Stis in teens and 20s, varied levels of immunity to meningococcal meningitis)
Gender (uti and anatomy, suppressed immunity in males)
Physiological state (preggers, puberty/menopause)
Pathological state (immunocompromised, low blood flow)
Drugs (PPIs, steroids)
Social (living cramped, damp)
Time (seasonal infections, incubation)
Place (current - e.g. Hospital, recent - e.g. Travel infections)
What are the two main categories of infection treatment? What can be done in each?
Specific - abx, surgery
Supportive - fluids, o2, pain relief, immunoglobulins, abx against proteins to reduce exotoxin production
What are the sirs criteria?
Give some examples of organ dysfunction seen in severe sepsis
Hypotension, confusion, decreased urine output, lactic acidosis
Why does sepsis alter coagulation?
What are the consequences
Cytokines initiate thrombin production and inhibit thrombolysis
Endothelial damage exposes TF and impairs prostacyclin production
DIC develops and clots can cause gangrene
What are the sepsis 6?
Within one hour:
Bloods for culture
IV fluids up
Urine output monitored
How is meningococcal meningitis subdivided?
What can we vaccinate against
Serogroups a,b, and c
Vaccines for a and c
What sort of a response does innate immunity provide to the body?
Fast and non specific
What are the first and second line defences of the innate immune system?
First - limits entry and growth
Second - contains and clears
What are the four categories of first line innate defences?
Physical - eg epithelial barrier, mucus membrane
Physiological - eg d/v coughing, sneezing
Chemical - eg stomach acid, vaginal acid, molecules (lysozymes, IgA, mucous, pepsin)
Biological - normal flora (compete, actively kill)
How does the stomach act as a chemical barrier to infection?
What is involved in second line innate defences?
What do phagocytes use to recognise pathogens?
Use pathogen recognition receptors (PRRs) to detect pathogen associated molecular patterns (PAMPs)
Examples of PAMPs with associated bacteria
Lipopolysaccerides (gram -ve)
Peptidoglycan (gram +ve)
Flagellin (flagella bacteria)
Mannose rich glycans (mycobacteria)
What can enhance recognition of bacteria by PRRs?
Opsinisation with C3b, C4b, IgG, CRP
In which bacteria is opsionisation vital?
Encapsulated bacteria - neisseria meningitidis, streptococcus pneumoniae
How does phagocytosis occur?
PRR recognises PAMP
Pseudopods engulph and ingest microbe forming phagosome
Phagosome fuses with lysosome
Microbe digested leaving residual body
Waste discharged from cell
How do phagocytes kill the microbes..
Lysozymes, lactoferrin, proteolytic enzymes
What chemical pathways are involved in second line innate immunity?
How is complement activated?
Classical pathway - antibody antigen complex
Alternative pathway - cell surface on microbes (e.g. LPS)
Mannose binding lectin - MBL binds to mannose on pathogen
What are the active components of compliment? What do they do?
C3a and C5a - chemotaxis
C3b and C4b - opsinisation
C5-C9 - membrane attack complexes
What are the effects of macrophage derived chemical in second line innate immunity?
Increase vascular permiability
Increase body temperature
What chemicials do macrophages release?
In what conditions are second line defences of innate immunity compromised?
Decreased neutrophils (leukaemia, chemotherapy)
Decreased neutrophil function
Define a healthcare related infection
An infection arising from a consequence of healthcare both within and out of hospital
How are hospital acquired infections differentiated form normal infections?
An infection that was neither present nor incubating at the time of admission (onset of symptoms >48 hrs after admission
What are the most common categories of healthcare related infections? What is the in hospital prevalence..
Gi and utis
What can we do to reduced healthcare related infections regarding patient factors?
Optimise physical health
Appropriate choice of medications (e.g. Decreased cephalosporins)
What can we do to reduced healthcare related infections regarding place factors?
Bed layout with siderooms for high risk patients
Pressure isolation rooms
Sink and toilets accessible and individual in high risk
Sterilisation and decontamination
What can we do to reduced healthcare related infections regarding practice factors?
Hospital policies (eg. No relative sitting on beds)
Leadership up to government level - incentives work
Healthcare worker vaccinations
What are the subdivisions of streptococcus?
Alpha haemolytic - pneumoniae and viridans
Beta haemolytic - pyrogenes
Non haemolytic - enterococcus
Diseases from strep viridans
Diseases from strep pyogenes
Diseases from strep pneumoniae
Diseases from staphylococcus
Treatment options for staphylococcus infection
Treatments for necrotising fasciitis
Initial broad spectrum like tazocin (pipperacillin and tazobactam)
Once id as strep pyogenes swich to ben pen
Large dose immunoglobulins to neutralise toxins
Antiprotein abx like clindamycin to decrease toxins
Debridment and amputation
Why is travel history important?
Different strains (resistance change and change in detecting)
What do you need to know about in a travel hx
Specific risks (sex, animals, swimming)
Preventative measures taken (prophylaxis, vaccinations, bite prevention)
What should you do with a suspected travel related infection?
Isolate until you know what it is!
Flag as high risk for lab
What are the causes of malaria?
What is the characteristic fever of malaria? Which subtype differs?
3 day cycling, malariae is 4 day cycling
Symptoms of malaria
Fever 3 day cycling
What is the usual incubation period for malaria?
What are the methods of transmission of malaria?
Vector - anaphalies mosquito in endemic region
Cryptic - mosi on a plane arriving at non endemic airport
Iatrogenic - infected equipment
What investigations would you perform in malaria?
U and e
What are the causative organisms of enteric fever?
Salmonella enterica typhi
Salmonella enterica paratyphi
How are Salmonella enterica typhi/paratyphi spread?
How can you reduce your risk?
Hand hygiene, safe food, vaccination
What treatments are effective in enteric fever?
Signs and symptoms of enteric fever
Constipation or diarrheoa
Intestinal haemorrhage and perforation
Investigations in suspected enteric fever
Stool and blood cultures
How do salmonella enterica typhi/paratyphi cause illness?
Fibriae adhere to epithelium over peyers patches
Invasin allows intracellular growth
As gram -ve have endotoxins
How can salmonella enterica typhi/paratyphi be distinguished in culture from escherichia coli?
They. Are non lactose fermenters
Otherwis both gram neg aerobic bacilli
What travel related infection is present in southern Europe?what is the causative organism?
How does brucellosis spread?
Spread via breaks in the skin and via the. Gi tract (e.g. Unpasturised milk)
Very rare person to person direct contact spread
How does brucellosis present?
Non specific flu like febrile illness
Bone and joint involvement
Long term complication endocarditis
How is brucellosis treated?
What are the two main components of adaptive immunity?
How is mhc adapted to a generalist presenting role?
Co dominant expression giving range of different subgroups
Peptide binding clefts very polymorphic
What is the difference in structure of mhc class 1 and class 2?
Class one - three alpha and one beta units
Class two - two alpha and two beta units
Note that the alpha and beta units are located on separate polypeptide chains.
What mhc molecule is active in cellular immunity? Which in humoural immunity?
Cellular - mhc 1 on most cells, both on apcs
Humoural - mhc 2 on apcs
How are cytotoxic t cells activated?
CD8 binds to MHC1 on an antigen presenting cell - presenting antigen recognised by t cell receptor
T cell binds to antigen on MHC1 on infected cell
Costimulation from IL2 produced by activated CD4 TH1 t cells
How do activated cd8 t cells kill the cell?
Release granzymes (protein digesting enzymes that trigger apoptosis)
Release granulysin and perforin (create channels in plasma membrane)
How does a t cell bind to a antigen presenting cell?
CD4/8 recognises MHC2/1. T cell receptor detects antigen in the MHC
How is an antigen attached to MHC1?
Sampling of cytosol
Proteins broken down by proteasome
Fragments released into ER
Fragment attached to MHC1
MHC1 moves to cell surface
How is an antigen attached to MHC2?
Pathogen phagocytosed by APC
Pathogen broken down by low pH and proteolysis
Vesicle of fragments merges with vesicle containing MHC2
Fragments load onto MHC2 and are moved to cell membrane
How are cd4 t cells activated?
Recognise and bind MHC2 on APC
Co stimulated by IL2 from APC
What do activated CD4 T cells do once activated?
TH1 - release IL 2 costimulating CD8 cells
TH2- costimulate b cells causing them to differentiate into plasma cells. Also activates eosinophils and mast cells
TH17 - activate neutrophils
What are the different antibodies?
What do they do?
G - opsinisation
A - mucosal immunity decreasing aggregation
M - initial response to novel antigen
E - on mast and basophils involved in allergic reaction/parasites
D - B cell receptor
What are the main functions of antibodies
Enhancing phagocytosis by opsionisation
Neutralisation of toxins
Complement activation (classical pathway)
In an infection what is the first antibody released? What is released on reinfection? What is different?
IgG much faster stronger and longer with a higher affinity
What are clinical uses of antibodies?
Active immunisations (e.g. Rabies)
Immediate protection (e.g. Post exposure hep b)
What would make a hiv patient a slow progressor?
MHC configured to present antigens of the virus that cannot be altered by the virus, thus the virus cant mutate and avoid being expressed.
What is the difference between HLA and MHC
MHC is the protein
HLA is the locus on the genome
How can HIV be subclassified generally? What is the epidemiology?
Hiv 1 - most common, nearly all western cases
Hiv 2 - confined to west africa, more indolent course
How is hiv 1 divided into groups?
M - major
N - new
O - outlier
How is group M of HIV 1 subclassified!!?
What is the clinical relevance?
A-K - CRF (circulating recombinant forms on co-infection)
West mainly B
Same tx but different response
What is the histological structure of the hiv virus?
SsRNA with reverse transcriptase
What is the lifecycle of HiV
Gp120 binds to CD4
Virus fuses with plasma expelling contents
Reverse transcriptase converts rna to dna
Dna intergrates into host genome
Production of viral mrna and proteins
Caspid assemble and buds from cell
At what point is a hiv infection irreversible?
Once the dna intergrates into the host genome
How long is the incubation period for HiV
What happens at the end of it?
How does hiv seroconversion present?
Only 25% ill enough to attend hcp
Non specific illness, fever, rash, sore throat, lymphadonopathy, headache
How many hiv infected people get seroconversion? What does it mean prognostically?
May be at risk of more accelerated disease course.
What is the term for the period between seroconversion and symptomatic hiv? What may be present?
What may be detectable in a hiv pt undergoing a seroconversion reaction?
Low cd4;cd8 ratio
Circulating viral rna
Viral p24 antigen
What causes symptomatic hiv?
How does it present?
Neurotoxins from hiv, cytokine abnormalities, low immunity
Aseptic meningitis, dementia, polyneuropathy, puritis, anaemia, anorexia, diarrhoea, weight loss ,
What are aids defining illnesses?
Candida of lower airways/oesophagus
What is the hiv core antigen?
What blood test will first show hiv?
Viral p24 antigen
2 to 8 weeks
What IgG tests can be used to detect hiv?
IgG to envelope - takes 3 months to build
IgG to core (p24) - detectible after weeks but lost as disease progresses
How are hiv antigens detected and assessed?
Elisa followed by western blotting
How would you not hiv test a baby of a infected mother?
Using IgG - it crosses the placenta so all babies will be positive
What are the general classes of antiretrovirals?
What is the term for the combination used in. hiv?
Reverse transcriptase inhibitors
What are the subtype of reverse transcriptase inhibitors?
Highly active antiretroviral therapy (haart)
What is a big side effect associated with NRTIs?
Effect mitochondria so lactic acidosis
What is the lifecycle of HBV?
Attaches to and enters hepatocyte
Looses coat and core enters nucleus
Processing of dna with reverse transcriptase
New virons enter blood
How is hepatic damage caused in hbv?
Immune response against virus
What are the immediate outcomes post infection with HBv? What percentage of patients do which?
Acute infections - clear (89%)
Acute infection - death (1%)
Acute infection - chronic infections (10%
What are the symptoms of acute hbv infection?
What causes death in acute hbv infection?
Fulminant hepatic failure
What age group is more likely to develop a chronic hbv infection?
Children (esp infants)
How can chronic hbv present?
Progressive - cirrhosis - risk of liver carcinoma
How do hbv antibodies change over the course of a disease with recovery?
Initial rise in HBs antigen and HBc IgG
HBs antigen falls
HBs IgG rises
How do hbv antibodies change in a chronic disease?
Rise and maintainance of HBc IgG and HBc antigen
If someone is vaccinated against hbv what antibody would you expect to be high? What would indicate that they had been infected?
If infected HBc antigen and IgG
How can HBV be prevented?
HBs antigen vaccination
PEP with immunoglobulin
Which infection can only occur alongside HBV? In what ways? What is different about the two ways of dual infection?
Coinfection - severe acute disease with low risk of chronic
Superinfection - reactivation of HBV with high risk of chronic
Why does HDV need HBV?
HDV uses envelope of HBV
In what ways can pathogens infect the internal surface of the body or prothesis?
Examples of each
Migration - Escherichia coli - UTI
Invasion - Streptococcus pyogenes - necrotising fasciitis
Haematogenous - streptococcus viridans - infective endocarditis
Innoculation - coag -ve staphylococcus - prothesis infection
What are the varying causes of infective endocarditis in native and prosthetic valves?
Native and >1 yr prosthetics - Strep. viridans, Staph. aureus, Candida
<1 yr prosthetics - coag -ve staphylococcus
What are the stages involved in the infection of a prothetic joint? How are bacteria adapted for this?
Adherence - pili/fimbriae
Biofilm formation - ecf production, quorum sensing (signalling for neighbours to produce ecf)
Invasion and multiplication
How do biofilms aid bacteria?
Protection from immune system
Protection from abx
Chemically favourable environment
What are the clinical problems regarding biofilms?
Poor abx penetration
Hard to grow as must shake loose first
Define hypersensitivity reactions
Inappropriate or excessive
Harm the host
What are the four types of hypersensitivity reaction?
Type 1 - antigen interacts with IgE on MAST cells triggering mediators inc. histamine release
Type 2 - drug attaches to cell membrane of RBC becoming a hapten then bound by antibodies activating complement causing cell lysis
Type 3 - antibody antigen complex not removed from blood by phagocytosis so keeps activating complement causing endothelial damage - can be especially bad if trapped in endothelium
Type 4 - activation t cells by hapten protein complex, causes skin inflammation and rash
What is the prevalence of allergy?
What is the most common?
How common is it?
What is the hygiene hypothesis?
Low pathogen exposure (clean living, small family, increased abx, low dirt)
Favours increased th2 cd4 t cells which instigate second phase of an allergic reaction
What do mast cells release? What do they do?
Histamine - smooth muscle dilation (arterioles) and constriction (bronchioles)
Cytokines - stimulate CD4 TH2, promote eosinophils and inflammation
Chemokines - attract inflammatory cells
Leukotrines - increase vascular permeability
How can a diagnosis of allergy be made?
Skin prick testing
Blood test for allergen specific IgE
What controls are used in skin prick testing?
Where does it test for reaction
Heparin and saline
What are the signs of epidermal allergy, dermis allergy?
Management of allergy
Education to recognise and get help
Emergency anaphylaxis tx.
What levels of disease can transmissable infection cause?
Endemic disease - normal background rate
Outbreak - 2 or more cases linked in time and place
Epidemic - a rate of infection greater that background rate
Pandemic - very high rate of infection across many countries and continents
How can we classify if a disease is going to increase in cases, remain constant or decrease in cases?
R0 number - the number of people one case infects
If more than 1 then numbers will increase
If 1 numbers will be constant
If less than 1 numbers will decrease
What could lead to an new increase in number of infections?
New pathogens - e.g. Mutation, spread
New person - e.g. Migration, newborn baby
New practice - e.g. Air conditioning
How do the general pattern of cases in epidemics and outbreaks differ?
Epidemics tend to follow a bell curve distribution of incidence against time
Outbreaks tend to follow a much more random distribution - they can be large with excellent control or small with non. This can lead to the false belief a certain intervention is effective even when it isn't
What is a paradox in polio control regarding immunisation? How can this paradox be applied to a western disease?
Those not immunised are exposed later in life and thus experience more severe disease (increased paralysis)
More adult chickenpox and thus increased infertility
What are problems with antibiotic resistance generally?
Resistance is irreversible
Development has stalled
Use causes resistance even if appropriate
What are the problems with abx resistance?
More severe treatments required
More expensive treatments required
What are the different classifications of resistance to abx?
Resistant - 1 or more agents in 1or 2 classes
Multi drug (MDR) - 1 or more agents in 3 or more classes
Extensively drug (XDR) - more than 1 agent in all but 2 classes
Pan drug (PDR) - all agents in all classes
What is the aim of abx stewardship?
Improve appropriate abx use
Achieve optimal clinical outcome
What clinicians are involved in ABX stewardship?
Infectious diseases physician
Infection control nurse
What types of intervention are there for antimicrobial stewardship?
Persuasive - education, consensus between clinicians, reminders, audits, feedback
Restrictive - limit abx on susceptability report, restrict formulary, require authorisation,
Structural - rapid lab tests to avoid general administration, computerised records
What type of abx stewardship intervention is most efficacious?
Initially restrictive but after several months both restrictive and persuasive
What are the outcomes seen from abx stewardship?
Non significant reduction in death rate
Significant reduction in length of stay
Significant increase in readmission (why!)
What is the pattern of infection seen in CF patients?
Birth - 3m = haemophillus influenzae
3m - 3y = staphylococcus aureus
3y - teens = pseudomonas aeruginosa
teens - 30s = atypical mycobacteria, candida, aspergillus
Why are cf patients more at risk of infection?
Lack of mucous clearence
Lung damage (bronchiectasis)
Why should cf cf contact be reduced?
Environmental psuedomonas tx is amenable to ABX but given time in a cf pt it develops ability to produce biofilm becoming much harder to treat - this can be spread to other cf patients
What pathogens are associated with copd exacerbations?
Haemophilus influenzae, pseudomonas aeruginosa, respiratory syncytial virus, parainfluenza virus, influenza A
Why are poorly controlled diabetics more at risk of infection?
Impaired humoural, neutrophil and lymphocyte function
Microvascular damage = poor tissue perfusion = damage
Neuronal damage = not noticing stimuli = damage
Sugar in urine = food for uti
What specific infections are associated with diabetes?
Malignant otitis externa
What are risk factors for uti in diabetics?
Increases glucose in urine
Neurogenic bladder that doesn't empty fully
What pathogens are prone to infecting diabetic foot ulcers?
Streptococcus pyrogenes (beta haemolytic)
What is malignant otitis externa?
Otitis externa with psuedomonas aerugenosa that can spread to neighbouring soft tissue and bone
What is rhinocerebral mucormycosis?
Mold fungi like aspergillus effecting paranasal sinuses invading blood vessels
Does downs syndrome effect risk of infection?
Yes - higher risk of urtis and lrtis due to altered structure of mouth and airways
What is an immunodeficiency?
A state in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
What immune system deficites (generally) can cause immunodeficiencey
What about an infection should make a clinician consider immunodeficiency?
S - severe
P - persistent
U - unusual
R - recurrent
Other than infection what are other issues with immunodeficiency?
Linked to autoimmune disease and malignancy
What are the categories of primary immunodeficiency? What are each group vulnerable too?
B cell - bacterial infection
T cell - viral (and fungal) infection
Complement - bacterial infection
Phagocyte - bacterial and fungal infection
What are the main B cell deficiencies?
Common variable immune deficiency
IgG subclass deficiency
What is CVID?
Common variable immunodeficiency
Inability of B cells to mature into plasma cells
What is brutons disease?
X linked agammagloblinaemia
Impaired b cell development with low igg and iga
Hw do b cell deficiencies present?
Recurrent bacterial urti and lrti
Lyphatic and gastric cancers
How do you treat b cell deficiencies
Avoidance of unnecessary radiation due to cancer risk
Give two t cell deficiencies
De georges syndrome
Severe combined immunodeficiency (SCID)
What are the problems in de georges syndrome
C - cardiac abnormalities
A - abnormal facies
T - thymic hypoplasia
C - cleft palate
H - hypocalcaemia
Tx of de georges syndrome
Bone marrow transplant
How do SCID diseases present?
Failure to thrive
Viral and fungal infections (PCP, CMV, VZV, EBV)
Skin and organ abcesses
Low t lymphocytes and decreased b activation so low ig
How do you treat SCID?
Reverse barrier nursing
Bone marrow transplant
How do complement deficiencies present?
Hereditory angioedema (C1 inhibitor deficiency)
Recurrent bacterial infections (C3 deficiency)
Neiserria infection (C5-7 deficiency)
What are the phagocyte deficiencies?
Leukocyte adhesion deficiency
Chronic granulomatous disease
Failure of phagosome formation
What is chronic granulomatous disease?
Lack of respiratory burst
How do phagocyte deficiencies present?
Bacterial and fungal infections of the skin, mucous membranes and lungs
How are phagocyte deficiencies treated?
Steroid/interferon gamma (chronic granulomatous disease)
Stem cell transplant
A young patient presents with a large number of persistent bacterial skin abscesses, what primary immunodeficiencies may he have? What tests would you like?
T cell deficiency
FBC, lymphocyte subset analysis, adhesion molecule expression, neutrophil function tests, IgG levels
What can cause primary immunodeficiencies?
Single gene disorders
What two general categories of secondary immunodeficiency are there? Examples?
Decreased production of immune component
- HIV, splenectomy, liver disease, malnutrition
Increased loss of immune components
- nephropathy, burns, enteropathy
What drugs can cause neutropenia?
Pheytoin, alcohol, chemotherapy, immunosuppressants
What diseases can cause neutropenia?
HIV, EBV, HBV, vit b deficiency, bone marrow cancer
Why might the spleen need removing?
Immune haemolytic disease
What disease can cause splenic atrophy?