Infection -MD2B3 Flashcards
what are the 3 domains of public health?
health improvement
health protection
health and social care quality
purpose of epidemiology
identify those at risk
assess effectiveness of interventions
determining importance of cause of illness
what is the triad of causal factors?
agent
host
environment
what is an epidemic/outbreak?
disease among specified population in excess of what’s expected in a given time and place
what is a cluster?
group of cases in a specific time and place - more than expected
what is an endemic?
disease or condition present among populations at all times e.g., malaria
what is a pandemic?
a disease or condition that spread across regions e.g., coronavirus, HIV
what is rate? and how is it calculated?
number of cases occurring during a specific period; dependant on size of population
number of cases/population at risk x 100
define prevalence
how common is the disease? established and new cases included
(NEW & EXISTING)
define incidence
rate at which new events occur over a defined period
NEW ONLY
What is R0?
the average number of cases of an infectious disease arising by transmission from a single infected individual in a population which hasn’t previously encountered the disease
how do you reduce infection spread
break the chain of infection
- infectious agents
- reservoirs
- portals of exit
- modes of transmission
- portals of entry
- susceptible hosts
types of investigations in outbreak management
- form outbreak control team (multidisciplinary team)
- microbiological investigation (food samples, culture, sequencing, susceptibility testing)
- environmental investigations (visit of premises, contaminated sites, observation practises, collection of samples)
- traceback investigations (FSA, food traceability, ‘farm to fork’, rapid alert system)
- veterinary investigations (Farm investigations, small animal practises)
- entomological investigations (vector borne diseases, mosquitos, sand flies, ticks, map distribution of vectors)
- gathering further information (identify info gaps, clinical details, lab results, trawling questionnaires)
- immediate control measures (prophylaxis, exclusion/isolation, public warning, withdrew of products, closing establishments…)
- communication (regular updates, keeping confidentiality, communicate public health messages, evaluate performance)
features of bacteria
no membrane bound organelles prokaryote dna PM cytoplasm ribosomes
name shapes of bacteria
cocci (spheres), bacilli (rods),
what is a bacterial colony?
group of bacteria derived from the same mother cell - genetically identical
describe bacteria by smell
bacteria produce different odours depending on the environment they’re in
electronic noses being developed to detect volatile substances
give example of bacteria and the smells they produce
candida spp. = yeast
clostridium difficile = fecal, putrid
nocardia spp. = musty basement
What bacteria have a purple appearance after staining?
gram positive
what bacteria are a reddish colour after gram staining?
gram negative
give an example of gram positive bacteria
staphylococci, streptococci and listeria
give examples of gram negative bacteria
enterococci, salmonella, pseudomonas
which gram bacteria have a thick peptidoglycan layer?
gram positive
which gram bacteria have an outer lipid membrane? (+/-)
gram negative
which gram bacteria have o-specific side chains present ? (+/-)
gram negative
what is a unique feature of gram negative bacteria?
Lipopolysaccharides (LPS)
antibiotics for example need to pass through this additional membrane before reaching targets inside cells therefore making them harder to treat.
they also have prions which enable transport in and out
what is a phototroph?
bacteria that utilise light as an energy source
e.g., cyanobacteria
what is a chemotroph?
bacteria that can only gain energy from chemical compounds
what do all bacteria require?
Carbon
and they all require CO2 in differing quantities
what category of bacteria use CO2 as their major or sole source of carbon?
Autotrophic bacteria
what category of bacteria use organic compounds as their carbon source?
heterotrophs
name some causes and types of mutations
during DNA replication - efficiency of repair mechanisms
silent, missense, nonsense, insertion/deletion
exposure to mutagens - radiation, chemical agents
what is the genome?
complete set of genetic material
what is a genotype?
full collection of genes in the genome
what is a phenotype?
observable characteristics and activities. defined by set of genes expressed at any one time
what genes are always expressed?
constitutive
What is the role of the promoter in gene regulation?
DNA sequence upstream of a gene where transcription machinery binds and initiates transcription
What is the role of activators in gene regulation?
increase transcription of a gene - keep a gene on
What is the role of repressors in gene regulation?
suppress transcription - keep a gene off
What is the role of inducers in gene regulation?
small molecules that can either activate or repress transcription by binding to repressors or activators
what is an operon?
sequence on the chromosome where structural proteins with related functions are usually encoded
simultaneous control of genes that will either all be needed at the same time or none will be needed
what is a regulon?
a group of several genes or operons that are turned on to off in response to the same signal by the same regulatory protein
what is pathogenicity?
the capacity to initiate disease - qualitative - all or nothing
what is virulence?
capacity to cause disease and severity of disease - quantifies pathogenicity
what is transmissibility?
ability of pathogen to transmit from human to human or reservoir to human
what are virulence factors?
proteins encoded by a bacterial organism that are essential for its pathogenicity - attribute the level of virulence
What are the 4 criteria to assess whether a microorganism causes a disease (postulates)?
- The microorganism is only found in the diseased individual
- the microorganism must be cultured from the diseased individual
- inoculation of the healthy individual with the cultured microorganism must cause the same disease
- microorganism must be re-isolated from the inoculated, diseased individual and match the original organism
what are the limitations of Koch’s 4 postulates?
assumes pathogens are only found in diseased individuals and not healthy individuals
not all pathogens can be grown in pure culture and not many human diseases can be reliably replicated in animal hosts so 3 and 4 can’t be applied
onset and severity of disease is dependant of the immune system of the host and their microbiome (postulate 3)
Not ethically appropriate to test pathogen on humans
steps to infection
transmission > adherence > invasion > survival in host > tissue damage
Features of secretion systems
- key virulence factor to several bacteria
- secrete molecules and virulence factors (effectors) out of bacteria cell to contact host
- T1SS, T3SS, T4SS, T6SS, T7SS can transfer proteins directly from cytoplasm to bacterial cell
- T2SS, T5SS, T8SS, T9SS can secrete proteins from the periplasm to the outside environment
- T3SS, T4SS, T6SS deliver proteins directly into the cytoplasm of host cell using specialised pili
which secretion systems are are specific to gram + bacteria?
T7SS
which secretion systems are are specific to gram - bacteria?
T3SS, T6SS
T3SS are related to flagella
stage 1 of infection
transmission
exposure of host to pathogen
usually reservoir
name some routes of entry for transmission
respiratory - droplet/airborne
GI - contaminated food, faecal - oral transmission
mucous membranes - absorption through urinary or genital tracts, exposed eyes, nose, mouth
skin - direct contact, open lesions, vector borne transmission
the second stage of infection is adhesion
what does this entail?
process which organisms attach themselves to cells (colonisation)
initial attachment is initiated by protein appendages - Fimbriae/pili/flagella
further mediated through exopolysaccharides - change hydrophobicity of bacteria surface and displaces water to enhance hydrophobic interactions - closer contact
a
attachment can also occur through production of proteins and polysaccharides expressed on cell surface - creation of biofilms which are stabilised by glycolax - hard to remove
describe the invasion step of infection
ECM creates physical stressors and host defence mechanisms against Bacteria
pathogens therefore produce proteins that induce entry into non-phagocytic target cells…
describe the zipper mechanism (invasion)
Bacteria express adhesins that bind with high affinity to host cell (interns, cadherins)
Triggers host into attempting to bind with another cell - cell junctions formed and spread around bacteria
bacterial cell is engulfed
e.g., helicobacter pylori, listeria monocytogenes
ZIPPER = ADHESINS AND CELL JUNCTIONS
describe the trigger pathway (invasion)
Bacterial effector proteins injected directly into host cell cytoplasm using T3SS
activates signalling pathway leading to large scale cytoskeletal rearrangement and ruffles formation
membrane ruffles around bacteria and fold over, engulfing and internalising the bacteria
e.g., salmonella, shigella
TRIGGER = EFFECTORS & RUFFLES
Survival in the host process (steps of infection)
vacuoles present hostile environment (low pH, nutrient deprived, target by host defences)
to replicate they need to adapt lifestyles
some escape from vesicle into cytoplasm where its more favourable (environmental cues)
bacteria express and secrete uptake systems - siderophores for iron uptake
evasion mechanisms - masking bacterial surface with host proteins (e.g., actin)
ability to trigger F-actin on surface to provide mechanical force to propel them through cytosol into neighbouring cells
Interfering with endosome maturation pathway - subvert host metabolism to modify membrane, present lysosomal fusion, import nutrients
what are the three categories of pathogens relating to level of dependance on host
obligate
facultative
extracellular
what are obligate pathogens?
require a host to fulfil their lifestyle - anaerobic bacteria (e.g.,chlamydia)
what is a facultative intracellular pathogen?
host is only one of the niches they can exploit to reproduce e.g., salmonella and shigella
what are extracellular pathogens?
thrive independently of a host cell e.g., S. aureus, E. coli
what is the final stage of infection and what does it involve?
tissue damage
In its effort to survive, replicate and find a new host, bacteria produce potent virulence factors that can cause tissue damage
primary mechanism = toxin production
toxins cause damage to host and can cause disease independent of bacterium
what are the 2 main types of toxins?
exotoxins - secreted and present in both gram positive and negative bacteria
endotoxins - Lipid A of lipopolysaccharides - Gram negative membrane
Features of exotoxins
heat liable immunogenic can be enzymatic - potent types -neurotoxin - tetanus -enterotoxin - diarrhoea -cytotoxin - lyse host cells
AB subunit arrangements
A: enzymatic activity
B: binding to specific receptor and transferring across host cell membrane
Enzymatic part not active until maturation of toxin - inactive while still in bacterium cell, active once secreted to avoid self damage
A + B synthesised separately
A - B synthesised separarlty but associated during secretion
A/B synthesised together but inactive until cleaved
pore forming toxins
-insert pores into host cell membrane e.g., S. aureus
superantigens
- toxins that stimulate the immune system
- act directly on T cells and antigen presenting cells
- impair their function and lead to disease
Features of endotoxins
toxic component of lipopolysaccharide (cell envelope, gram - bacterium)
not a protein
heat stable
weakly antigenic - no vaccine
not enzymatic - need high doses
associated with endotoxic shock
LPS degrades into O-antigen and Lipid A
-Lipid A is pro-inflammatory and activates a cascade
- loss of production control of host cell can lead to fever, or systemic shock and intravascular coagulation
what is the natural history of a disease?
describes the expected progression of disease over time from first point of infection onwards
(what symptoms in what order)
what is the incubation period?
time between infection and symptom onset
What is the latent period of a disease?
Time between person being infected and when they start being infectious
what is the infectious period of a disease?
period of time a person is infectious
three parts of descriptive epidemiology
Time - is the disease seasonal, pattern of disease changing over time?
Place- does pattern of disease vary by place?
Person - who is at risk, Age, occupation… who is more susceptible
what are prevention strategies?
Primary - vaccination, limit salt intake, hand washing, healthy lifestyle
Secondary - breast cancer screening, reduce risk of harm from disease, prompt treatment, early intervention
Tertiary - prevent complications from the disease, diabetic eye screening, drugs to reduce risk of another stroke
what is a case definition and why is it important?
important to have a clear definition of a case so their is consistency in the public health actions taken
important for surveillance so you know you’re counting the same disease in different areas
might be based in different types of criteria
-clinical criteria - signs and symptoms
-microbiological criteria - lab tests
-radiological criteria - x ray
-epidemiological criteria - known link to confirmed case
disease will have different definitions for possible, probable and confirmed cases
- level of certainty will affect actions taken - balance benefits and harms and using resources
- need a response proportionate to public health risk
Bacteria of key public importance - Neisseria meningitides
gram negative aerobic diplococcal lives harmlessly in nose and throats of ~1 in 10 people can cause meningitis and septicaemia
Mode of transmission = person to person (kissing, household, close proximity)
Natural History = incubation period of 3-5 days
Clinical features = fever, cold hands and feet, vomiting, diarrhoea, difficult to wake, confusion
Complications = 10% case fatality rate, permanent complications in ~15% of survivors
Epidemiology
Time - Meningococcal disease is seasonal - more common in winter
Decrease in group c following vaccine -1999
place - higher incidence in belt spanning widest part of Africa
person - overcrowding, smoking, recent flu, immune conditions, no spleen, 1-5 yrs or teenagers
Prevention
Primary - vaccination
Secondary - rapid medical treatment, raise awareness of symptoms.
Tertiary - antibiotics, intramuscular benzylpenicillin
Public health management notifiable disease check patient has been taken to hospital assess likelihood case is meningitis if conformed case contacts contacted case contacts tracked contacts offered chemoprophylaxis offered vaccine
what is a cluster?
household cluster: 2 or more cases within 28 days within the same household. should be offered relevant vaccine sonf chemoprophylaxis
residential/educational clusters: 2 or more cases within 28 days within an educational/residential setting
Bacteria of key public importance- chlamydia trachomatis
Gram negative 3 biovars -thrachoma -chlamydia -lymphogranuloma venereum
causes chlamydia
risk of neonatal conjunctivitis and pneumonia (child born to infected mothers)
cause trachoma - eye infection leading to blindness
chlamydia
Mode of transmission = sexual - unprotected, sharing unwashed sex toys…
= vertical - mother to baby at birth
Natural History = incubation period - 1-3 weeks
= often asymtomatic
= 7 in 10 women and 5 in 10 men experience no symptoms
clinical features = pain when urinating, unusual discharge
= women - bleeding after sex, bleeding between periods
= men - burning/itching urethra
complications = fertility issues, ectopic pregnancy risk, men - sexually acquired reactive arthritis
epidemiology
time - detection fell in 2020, decline in test coverage, high volume of screening required, true prevalence in population will be higher, more testing = more cases
place- detection rates in young people are higher in more deprived areas than least
person - sexually active young people (under 25) most at risk, multiple partners with lack of condom use
prevention
primary- promote safe sex, condom use. no vaccines
secondary - screening for asymptomatic individuals, raising awareness, reccomended getting tested once a year is sexually active with new partners
tertiary - treatment with antibiotics, sex avoided until treatment has taken effect
public health management
not a notifiable disease
contact tracing - advise partners to be tested.
Bacteria of key public importance- Legionella pneumophila
gram negative bacterium
rod shaped
lives in water sources - infect humans when the infected water is aerosolised
associated with legionnaires disease, can be fatal
facultative intracellular bacterium
mode of transmission = inhalation of bacteria via aerosols
natural history = incubation period - 2-10 days before symptom onset (usually 6-7)
no infection period as its not transmissible between humans
clinical features = pneumonia, fever, dry cough, fatigue, head and muscle aches
complications = case fatality rate of ~10% in Europe
epidemiology
time- seasonality, summer, early autumn, relate to weather patterns
place- 2019, 48% of cases were community associated, 2% healthcare associated, 40% travel abroad, 10% uk travel
Spain and UAE
person - older age, male sex, recent travel, smoking, cv or respiratory disease
prevention/treatment
high quality water management
biofilms protect pathogen but if broken up, it can travel with the water
cooling towers are a risk as they spread the bacteria over a large distance. operate at ideal temperatures for pathogen to grow
treatment - antibiotics, managing complications
public health management of disease
notifiable disease
ascertain likely sources of infection and putting control measures in place
source not person is focus of public management
enhanced surveillance questionnaires too locate source
Bacteria of key public health importance - Escherichia coli
gram- negative bacterium
STEC and VTEC produce toxins that cause disease
Reservoir is the digestive tract of ruminants - grazing animals with 4 part stomachs
most well known STEC group is E. coli O157 - grouped based on O antigen
can also be grouped based on H antigen - E. coli O157:H7
STEC causes GI illness and the E. coli can also cause bloodstream infections in vulnerable patients
mode of transmission = food or water borne, or faecal oral transmission (animal or human)
key risks - uncooked salad vegetables, uncooked meat, unpasteurised milk, water based activities, farm visits
Natural History = incubation period of 3-4 days
prolonged infectiousness through shedding of bacteria in stools
clinical features = some may be asymptomatic or diarrhoea, abdominal cramps, vomiting
complications = heamolytic uraemia syndrome - caused by STEC toxins killing RBCs. Makes patients anaemic and cause kidney issues and long term kidney damage, Gastroenteritis, high mortality rate(10%)
epidemiology
time - seasonal pattern - more cases over summer than winter
place - northeast England has highest cases, London has the lowest
person - young people most at risk. 58% of cases were female in 2018
prevention
appropriate water management and treatment
hand washing after contact with animals
food hygiene measures
free of symptoms for 48 hours before returning back to school
treatment
replacing fluids
public health management strategies
different actions depending on the certainty of diagnosis (possible, probable, confirmed)
enhanced surveillance questionnaires - symtoms experienced, places travelled to , food outlets, water sources, contact with animals
risk assessment for transmission
outbreak management
OCT
investigations, finding source, surveillance, managing cases, control measures
Bacteria of key public importance - clostridium difficile
gram positive + anaerobic rod shaped forms spores - allows survival in places cells can't lives in digestive tract produces disease causing toxins
Causes C.diff infection
mode of transmission = faecal oral route, ingestion of spores
natural history = lives inside people without causing any problems however when people are given antibiotics it can kill off other bacteria in the digestive tract and allow C. difficile to proliferate allowing the toxins to reach levels where they can cause disease
clinical features = diarrhoea, fever, loss of appetite, nausea, abdominal pain
complications = pseudomembranous colitis - 13.5% fatality rate 2019/20
Epidemiology
Time - incidence and death rate has decreased dramatically since 2007 could be due to infection control interventions e.g., hand washing, guidance for antibiotic prescribing
Place - contaminates environment due to pores. in a hospital it can quickly spread between vulnerable patients,
Person - antibiotic use, old age
Prevention
good antibiotic prescribing practise
infection control measures - isolate infected individuals, PPE, contractually NHS trusts have to keep infections below 10
Treatment
antibiotics and supportive care to avoid dehydration
public health management
prevent person to person spread among vulnerable people
SIGHT accronym
S - suspect case is infectious where there is no other cause of diarrhoea
I- isolate patient and consult with ICT
G - gloves and aprons used for all contact with patients
H - hand washing
T - test stool for toxin
Bacteria of key public importance - clostridium difficile
gram positive + anaerobic rod shaped forms spores - allows survival in places cells can't lives in digestive tract produces disease causing toxins
Causes C.diff infection
mode of transmission = faecal oral route, ingestion of spores
natural history = lives inside people without causing any problems however when people are given antibiotics it can kill off other bacteria in the digestive tract and allow C. difficile to proliferate allowing the toxins to reach levels where they can cause disease
clinical features = diarrhoea, fever, loss of appetite, nausea, abdominal pain
complications = pseudomembranous colitis - 13.5% fatality rate 2019/20
Epidemiology
Time - incidence and death rate has decreased dramatically since 2007 could be due to infection control interventions e.g., hand washing, guidance for antibiotic prescribing
Place - contaminates environment due to pores. in a hospital it can quickly spread between vulnerable patients,
Person - antibiotic use, old age
Prevention
good antibiotic prescribing practise
infection control measures - isolate infected individuals, PPE, contractually NHS trusts have to keep infections below 10
Treatment
antibiotics and supportive care to avoid dehydration
public health management
prevent person to person spread among vulnerable people
SIGHT acronym
S - suspect case is infectious where there is no other cause of diarrhoea
I- isolate patient and consult with ICT
G - gloves and aprons used for all contact with patients
H - hand washing
T - test stool for toxin
steps of an outbreak investigation
- establish existence of a real outbreak
- convene an outbreak control team
- confirm diagnosis
- define a case
- search for cases / case finding
- generate hypothesis - descriptive epidemiology
- environmental, laboratory and other investigations
- test hypothesis using analytical epidemiology
- draw conclusions
- communicate findings
what is an outbreak?
single case for certain rare disease
suspected, anticipated or actual event
2 or more people experiencing a similar illness and are linked in time and place
greater than expected rate of infection
what is an outbreak?
single case for certain rare disease
suspected, anticipated or actual event
2 or more people experiencing a similar illness and are linked in time and place
greater than expected rate of infection
what are the aims of investigation by outbreak control team?
assess the risk to public
agree and coordinate response with stakeholders
describe the outbreak in terms of time, place and person
generate and test the hypothesis
identify the source/vehicle of infection
implement control measures
what are the main types of surveillance?
passive - you are notified
stimulated passive - phone-calls / visits to facilities to trigger reporting
active surveillance - search for records in healthcare facilities, door to door, potting possible cases
what are features of a trawling questionnaire and what is it used for?
Used for generating a hypothesis
includes
- open ended questions
- conducted by EHO’s, health protection agency…
- aims to identify
- what is common to all cases,
- symptoms and time of onset
- events participated in
- place visited
- any outliers? - are they the source? problem with data collection?
what is a line list used for?
collates cases in a systematic way and highlights time, place, person and lab results, allows generation of epidemic curve
epidemiological curves
common source - intermittent or continuous
point source - outbreak at defined point in time
propagated source - person to person transmission
what is a point source?
one common source, people ill at same time, one event e.g., wedding. one incubation period
what is a continuous source?
source is not eradicated or controlled, single exposure over a long period
what is a propagated source?
people infecting others, spread.
one case > incubation period > higher peak, then another group etc - secondary and tertiary cases
what is an intermittent source?
periodic infection
source is still coming through
concurrent
e.g., delivery of infected vegetables periodically
all exposed to common source
not well controlled so outbreaks reoccur
when is a cohort study used?
in food outbreaks where population is known and available
e.g., wedding reception
allows attack rate and relative risk (RR) to be calculated
when is a case control study used?
in large, exposed populations compares 'case' exposures or behaviours with controls odds ratio (OR)
name some common control measures
- remove the source - isolate and treat cases, destroy implicated foodstuffs from food chain
- protect persons at risk - infection control, prophylaxis
- prevent reoccurrence - local recommendations, national guidelines
describe the innate response
fast directly detect an infectious agent through receptors/sesors genetically encoded memoryless no improvement over time
involves macrophages, dendritic cells and neutrophils (phagocytic cells)
remove the microbe and destroy it
describe the adaptive response
slower memory to previous encounters T cell and B cells somatic gene recombination capacity to recognise almost any pathogen
what is the role of T cells in the adaptive immune response?
they initiate it
help other immune cells - T helper cells
kill infected cells by direct recognition - Cytotoxic T cells
T cell interaction with peptide MHC is the molecular bridge between innate and adaptive response
Name some epithelial barriers
skin epidermis
bronchial ciliated epithelium,
gut epithelium
name some chemical barriers to infection
Lysozyme in tears and saliva
surfactants in lungs
stomach acid
mucous in respiratory, GI and GU tracts
what are pattern recognition receptors?
Proteins capable of recognising molecules frequently found in pathogens
name some membrane bound Protein Recognition Receptors (PRRs)
Toll like receptors
C- type receptors
what drives the expression of adhesion proteins on blood vessel cells?
inflammation
What are lymphocyte antigen receptors?
use somatic gene recombination to create sequence diversity so almost limitless potential receptors can be encoded
(T and B cell reeceptors) are not genetically encoded
what is inflammation?
response to infection/injury of vascularised tissues. to eliminate dying cells and foreign bodies
What is the set point of the immune system?
its crucial for healthy homeostasis
tolerance
what happens during a bacterial infection?
subvert immune response or hijack it
what is a PAMP?
pathogen associated molecular patterns
what structures are found in/on stressed dying/dead host cells?
DAMPS
damage associated molecular patterns
what is antigenic drift and why is it important?
its a point amino acid mutation in key proteins
its the driver of seasonal variation
what is antigenic shift?
significant alteration in sequence often by capturing genetic sequences from closely related virus
what allows viruses avoid immune evasion?
latency periods e.g., herpes virus. allows the virus to hide in the host genome and doesn’t provide any antigens for presentation
what is the virus that leads to AIDS?
human immunodeficiency virus 1 - lent virus
how does chronic AIDS develop?
positive feedback from inflammation
inability to clear self antigens
broadening of immune response
name some treatments for autoimmunity
costimulatory blockade - inhibits T cell activation (e.g., RA)
corticosteroids
immunosuppressants
monoclonal antibodies
what is a primary immune deficiency? - PID
born with a faulty immune system - congenital
results from genetic mutations
is a secondary immune deficiency: congenital or acquired? (SID)
Acquired
what is a SCID?
Severe combined immunodeficiency
range of significant PIDS that cause defects in the adaptive immune response
patients often come from consanguineous families (incest)
what are potential origins of non self tumour antigens?
neoantigens formed by gene splicing
aberrant expression of immune privileged antigens
abnormal post translational modification to proteins that aid tumorgenesis
oncoviral proteins
what is CAR therapy?
inserts cancer targeting receptor Inyo T cells using lentiviral transduction ex vivo
success in B cell acute leukaemia - 90% remission
risk of cytokine storm and outgrowth of tumours
when would a cohort study be used?
outbreak investigation in a well-defined population - able to identify full population potentially exposed
cohort is a group of people with something in common
what is attack rate?
proportion of people who become ill with a disease who were initially free
number of cases/total number of participants x 100
calculate attack rates for exposed and unexposed individuals
what is the risk ratio/relative risk?
ratio of exposed and unexposed attack rates
what is relative risk?
risk of disease in exposed/risk of disease in unexposed
this determines if the attack rate in the exposed is higher than the attack rate and by how many times
what does it mean if the risk ratio is greater than 1
the agent in question is a risk factor (more exposed than unexposed were positive cases)
what does it mean if the risk ratio is = to 1
no association between agent and disease
what does it mean if the RR= less than 1
the agent in question is a protective factor against the disease
when is a case control study used?
when there is not a defined population
e.g., an increase in cases in a particular geographical area
are all cases included in a case control study?
yes and then controls are selected
what is an odds ratio?
estimates the difference in frequency of exposure between cases and controls (from the same population)
odds=probability an event will/will not happen
what does it mean if the odds ratio is greater than 1
the agent is a risk factor (e.g., chicken)
the higher the risk factor the stronger the association
what does it mean when the odds ratio is equal to 1?
there is no association between the agent and the disease
what does it mean when the odds ratio is less than 1
the agent is a protective factor
what is a p-value?
probability of obtaining a result at least as extreme as the observed results assuming the null hypothesis is correct
what is the null hypothesis?
no association between the cases and the exposure
in what situation would we reject the null hypothesis?
if the p value is low (below 0.05/5%) we can say the association between factor and disease is likely to be real hence there is an association between cases and exposure and so the null hypothesis is rejected
what does a p value below 0.05 indicate?
strong evidence against the null hypothesis
statistically significant association between the cases and exposure
what are confidence intervals?
range of potential values for the RR or OR calculated from a sample
a confidence interval indicates the precision with which the sample estimate is likely to represent the population from which that sample was drawn
what does a 95% confidence interval mean?
for a 95% confidence interval the true value for the population at large will lie within the range 19 times out of 20 (95/100)
a narrow CI implies a large sample size
what does it mean if a confidence interval includes 1?
no evidence at the level of a p=0.05 that there is a true difference
what is a confounder?
something that is associated with both the exposure and the outcome
what is multivariable analysis?
looks at the the associations for several x variables (exposures) simultaneously but only 1 Y variable. is it the combination causing the disease?
what is regression analysis?
set of statistical processes for estimating the relationships between a depending variable/outcome and one or more independent variables.
what is an adjusted odds ratio?
controls for other variables - produces an odds for rich variable assuming the other variables were held constant
how much do hospital acquired infections cost the NHS annually?
£1 billion
and 300000 patients
what are features of S. aureus?
gram positive coccus staphylo clusters - grape like produce coagulase - blood clotting enzyme facultative anaerobe (w/without oxygen)
what percentage of the population carry s. aureus?
30% - skin and nose in healthy individuals
how does s.aureus cause infection?
adhesion
invasion
biofilm formation
intracellular survival within cells
describe the adhesion step of s.aureus infection
adhesion to the host epithelium or mucosal lining of the skin or nares.
bacteria have several adhesins e.g., fibrinogen binding proteins, clumping factor A, which bind to host cell receptors
describe the invasion step of s.aureus infection
when there is a breach in the epithelial layer s. aureus is able to penetrate to the lower layers of the tissue
here the tissue resident macrophages and phagocytes such as neutrophils are recruited to the site of infection
these phagocytose the bacteria and kill them. the local immune response leads to the formation of an abscess.
however if the immune cells are not successful, the pathogen can invade deeper into tissues and eventually the blood stream
describe the biofilm formation step of s.aureus infection
s. aureus can form biofilms on tissues and medical devices such as catheters
antibiotics cannot penetrate biofilms efficiently and so are hard to treat effectively
describe the intracellular survival of s.aureus within cells
its a facultative intracellular pathogen so can enter different types of host cells, including immune cells such as macrophages
bacteria can replicate and then eventually lyse the cells to disseminate, or they can persist in this niche for longer times
drugs cannot kill intracellular bacteria effectively
name some infections caused by s.aureus
skin and soft tissue bone and joint - e.g., osteomyelinitis infective endocarditis pneumonia medical device or implant related q
what drug is s. aureus resistant to?
beta-lactam - penicillin
how many deaths were related to MRSA infection in the UK in 2018-19?
12878
how does S. aureus become resistant to drugs?
modification of drugs target
enzymatic inactivation of the drug and active efflux of the drug
what is endogenous spread of s. aureus?
when the patient is already colonised by the bacteria and it spreads to another part of the body
what is exogenous spread of s. aureus?
from person to person
direct contact with skin, equipment or other surfaces
name control measures hospitals use to prevent MRSA spread
hand hygiene
general premises cleanliness
covering wounds and lesions
appropriate PPE
what are the features of acinetobacter baumannii?
gram-negative rod shaped aerobic bacteria found in soil and water resistant to desiccation and dry conditions
virulence mechanisms of A. baumannii
surface adhesions
resistance to disinfection and desiccation
it can pum disinfectant out of cell through efflux protein Ace-1
low alcohol concentrations can make it more virulent
stats and facts about a. baumannii
causes 2% of HAIs globally
infects the skin and mucous membranes
major cause of infections in the army - survive in dry and sandy conditions
cause pneumonia, blood stream infections, septicemia, UTIs
what are the 4 mechanims of resistance of A.baumannii?
beta-lactam hydrolysis
modification of aminoglycosides - inactivate antibiotics
active efflux mechanisms - pump out antibiotics
changing outer membrane - modify lipid A composition - deter binding
