Infection -MD2B3 Flashcards

1
Q

what are the 3 domains of public health?

A

health improvement
health protection
health and social care quality

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2
Q

purpose of epidemiology

A

identify those at risk
assess effectiveness of interventions
determining importance of cause of illness

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3
Q

what is the triad of causal factors?

A

agent
host
environment

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4
Q

what is an epidemic/outbreak?

A

disease among specified population in excess of what’s expected in a given time and place

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5
Q

what is a cluster?

A

group of cases in a specific time and place - more than expected

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6
Q

what is an endemic?

A

disease or condition present among populations at all times e.g., malaria

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7
Q

what is a pandemic?

A

a disease or condition that spread across regions e.g., coronavirus, HIV

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8
Q

what is rate? and how is it calculated?

A

number of cases occurring during a specific period; dependant on size of population
number of cases/population at risk x 100

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9
Q

define prevalence

A

how common is the disease? established and new cases included

(NEW & EXISTING)

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10
Q

define incidence

A

rate at which new events occur over a defined period

NEW ONLY

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11
Q

What is R0?

A

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

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12
Q

how do you reduce infection spread

A

break the chain of infection

  • infectious agents
  • reservoirs
  • portals of exit
  • modes of transmission
  • portals of entry
  • susceptible hosts
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13
Q

types of investigations in outbreak management

A
  1. form outbreak control team (multidisciplinary team)
  2. microbiological investigation (food samples, culture, sequencing, susceptibility testing)
  3. environmental investigations (visit of premises, contaminated sites, observation practises, collection of samples)
  4. traceback investigations (FSA, food traceability, ‘farm to fork’, rapid alert system)
  5. veterinary investigations (Farm investigations, small animal practises)
  6. entomological investigations (vector borne diseases, mosquitos, sand flies, ticks, map distribution of vectors)
  7. gathering further information (identify info gaps, clinical details, lab results, trawling questionnaires)
  8. immediate control measures (prophylaxis, exclusion/isolation, public warning, withdrew of products, closing establishments…)
  9. communication (regular updates, keeping confidentiality, communicate public health messages, evaluate performance)
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14
Q

features of bacteria

A
no membrane bound organelles
prokaryote
dna
PM
cytoplasm 
ribosomes
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15
Q

name shapes of bacteria

A

cocci (spheres), bacilli (rods),

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16
Q

what is a bacterial colony?

A

group of bacteria derived from the same mother cell - genetically identical

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17
Q

describe bacteria by smell

A

bacteria produce different odours depending on the environment they’re in
electronic noses being developed to detect volatile substances

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18
Q

give example of bacteria and the smells they produce

A

candida spp. = yeast
clostridium difficile = fecal, putrid
nocardia spp. = musty basement

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19
Q

What bacteria have a purple appearance after staining?

A

gram positive

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20
Q

what bacteria are a reddish colour after gram staining?

A

gram negative

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21
Q

give an example of gram positive bacteria

A

staphylococci, streptococci and listeria

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22
Q

give examples of gram negative bacteria

A

enterococci, salmonella, pseudomonas

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23
Q

which gram bacteria have a thick peptidoglycan layer?

A

gram positive

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24
Q

which gram bacteria have an outer lipid membrane? (+/-)

A

gram negative

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25
which gram bacteria have o-specific side chains present ? (+/-)
gram negative
26
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
27
what is a phototroph?
bacteria that utilise light as an energy source | e.g., cyanobacteria
28
what is a chemotroph?
bacteria that can only gain energy from chemical compounds
29
what do all bacteria require?
Carbon | and they all require CO2 in differing quantities
30
what category of bacteria use CO2 as their major or sole source of carbon?
Autotrophic bacteria
31
what category of bacteria use organic compounds as their carbon source?
heterotrophs
32
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
33
what is the genome?
complete set of genetic material
34
what is a genotype?
full collection of genes in the genome
35
what is a phenotype?
observable characteristics and activities. defined by set of genes expressed at any one time
36
what genes are always expressed?
constitutive
37
What is the role of the promoter in gene regulation?
DNA sequence upstream of a gene where transcription machinery binds and initiates transcription
38
What is the role of activators in gene regulation?
increase transcription of a gene - keep a gene on
39
What is the role of repressors in gene regulation?
suppress transcription - keep a gene off
40
What is the role of inducers in gene regulation?
small molecules that can either activate or repress transcription by binding to repressors or activators
41
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
42
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
43
what is pathogenicity?
the capacity to initiate disease - qualitative - all or nothing
44
what is virulence?
capacity to cause disease and severity of disease - quantifies pathogenicity
45
what is transmissibility?
ability of pathogen to transmit from human to human or reservoir to human
46
what are virulence factors?
proteins encoded by a bacterial organism that are essential for its pathogenicity - attribute the level of virulence
47
What are the 4 criteria to assess whether a microorganism causes a disease (postulates)?
1. The microorganism is only found in the diseased individual 2. the microorganism must be cultured from the diseased individual 3. inoculation of the healthy individual with the cultured microorganism must cause the same disease 4. microorganism must be re-isolated from the inoculated, diseased individual and match the original organism
48
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
49
steps to infection
transmission > adherence > invasion > survival in host > tissue damage
50
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
51
which secretion systems are are specific to gram + bacteria?
T7SS
52
which secretion systems are are specific to gram - bacteria?
T3SS, T6SS | T3SS are related to flagella
53
stage 1 of infection
transmission exposure of host to pathogen usually reservoir
54
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
55
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
56
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...
57
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
58
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
59
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
60
what are the three categories of pathogens relating to level of dependance on host
obligate facultative extracellular
61
what are obligate pathogens?
require a host to fulfil their lifestyle - anaerobic bacteria (e.g.,chlamydia)
62
what is a facultative intracellular pathogen?
host is only one of the niches they can exploit to reproduce e.g., salmonella and shigella
63
what are extracellular pathogens?
thrive independently of a host cell e.g., S. aureus, E. coli
64
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
65
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
66
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
67
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
68
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)
69
what is the incubation period?
time between infection and symptom onset
70
What is the latent period of a disease?
Time between person being infected and when they start being infectious
71
what is the infectious period of a disease?
period of time a person is infectious
72
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
73
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
74
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
75
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 ```
76
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
77
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.
78
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
79
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
80
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
81
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
82
steps of an outbreak investigation
1. establish existence of a real outbreak 2. convene an outbreak control team 3. confirm diagnosis 4. define a case 5. search for cases / case finding 6. generate hypothesis - descriptive epidemiology 7. environmental, laboratory and other investigations 8. test hypothesis using analytical epidemiology 9. draw conclusions 10. communicate findings
83
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
84
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
85
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
86
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
87
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?
88
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
89
epidemiological curves
common source - intermittent or continuous point source - outbreak at defined point in time propagated source - person to person transmission
90
what is a point source?
one common source, people ill at same time, one event e.g., wedding. one incubation period
91
what is a continuous source?
source is not eradicated or controlled, single exposure over a long period
92
what is a propagated source?
people infecting others, spread. | one case > incubation period > higher peak, then another group etc - secondary and tertiary cases
93
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
94
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
95
when is a case control study used?
``` in large, exposed populations compares 'case' exposures or behaviours with controls odds ratio (OR) ```
96
name some common control measures
1. remove the source - isolate and treat cases, destroy implicated foodstuffs from food chain 2. protect persons at risk - infection control, prophylaxis 3. prevent reoccurrence - local recommendations, national guidelines
97
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
98
describe the adaptive response
``` slower memory to previous encounters T cell and B cells somatic gene recombination capacity to recognise almost any pathogen ```
99
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
100
Name some epithelial barriers
skin epidermis bronchial ciliated epithelium, gut epithelium
101
name some chemical barriers to infection
Lysozyme in tears and saliva surfactants in lungs stomach acid mucous in respiratory, GI and GU tracts
102
what are pattern recognition receptors?
Proteins capable of recognising molecules frequently found in pathogens
103
name some membrane bound Protein Recognition Receptors (PRRs)
Toll like receptors | C- type receptors
104
what drives the expression of adhesion proteins on blood vessel cells?
inflammation
105
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
106
what is inflammation?
response to infection/injury of vascularised tissues. to eliminate dying cells and foreign bodies
107
What is the set point of the immune system?
its crucial for healthy homeostasis | tolerance
108
what happens during a bacterial infection?
subvert immune response or hijack it
109
what is a PAMP?
pathogen associated molecular patterns
110
what structures are found in/on stressed dying/dead host cells?
DAMPS | damage associated molecular patterns
111
what is antigenic drift and why is it important?
its a point amino acid mutation in key proteins | its the driver of seasonal variation
112
what is antigenic shift?
significant alteration in sequence often by capturing genetic sequences from closely related virus
113
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
114
what is the virus that leads to AIDS?
human immunodeficiency virus 1 - lent virus
115
how does chronic AIDS develop?
positive feedback from inflammation inability to clear self antigens broadening of immune response
116
name some treatments for autoimmunity
costimulatory blockade - inhibits T cell activation (e.g., RA) corticosteroids immunosuppressants monoclonal antibodies
117
what is a primary immune deficiency? - PID
born with a faulty immune system - congenital | results from genetic mutations
118
is a secondary immune deficiency: congenital or acquired? (SID)
Acquired
119
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)
120
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
121
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
122
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
123
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
124
what is the risk ratio/relative risk?
ratio of exposed and unexposed attack rates
125
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
126
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)
127
what does it mean if the risk ratio is = to 1
no association between agent and disease
128
what does it mean if the RR= less than 1
the agent in question is a protective factor against the disease
129
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
130
are all cases included in a case control study?
yes and then controls are selected
131
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
132
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
133
what does it mean when the odds ratio is equal to 1?
there is no association between the agent and the disease
134
what does it mean when the odds ratio is less than 1
the agent is a protective factor
135
what is a p-value?
probability of obtaining a result at least as extreme as the observed results assuming the null hypothesis is correct
136
what is the null hypothesis?
no association between the cases and the exposure
137
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
138
what does a p value below 0.05 indicate?
strong evidence against the null hypothesis | statistically significant association between the cases and exposure
139
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
140
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
141
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
142
what is a confounder?
something that is associated with both the exposure and the outcome
143
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?
144
what is regression analysis?
set of statistical processes for estimating the relationships between a depending variable/outcome and one or more independent variables.
145
what is an adjusted odds ratio?
controls for other variables - produces an odds for rich variable assuming the other variables were held constant
146
how much do hospital acquired infections cost the NHS annually?
£1 billion | and 300000 patients
147
what are features of S. aureus?
``` gram positive coccus staphylo clusters - grape like produce coagulase - blood clotting enzyme facultative anaerobe (w/without oxygen) ```
148
what percentage of the population carry s. aureus?
30% - skin and nose in healthy individuals
149
how does s.aureus cause infection?
adhesion invasion biofilm formation intracellular survival within cells
150
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
151
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
152
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
153
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
154
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 ```
155
what drug is s. aureus resistant to?
beta-lactam - penicillin
156
how many deaths were related to MRSA infection in the UK in 2018-19?
12878
157
how does S. aureus become resistant to drugs?
modification of drugs target | enzymatic inactivation of the drug and active efflux of the drug
158
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
159
what is exogenous spread of s. aureus?
from person to person | direct contact with skin, equipment or other surfaces
160
name control measures hospitals use to prevent MRSA spread
hand hygiene general premises cleanliness covering wounds and lesions appropriate PPE
161
what are the features of acinetobacter baumannii?
``` gram-negative rod shaped aerobic bacteria found in soil and water resistant to desiccation and dry conditions ```
162
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
163
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
164
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
165
what drug is used to treat a. baumannii infections
carbapenem antibiotic
166
name theraputic options for a. baumannii treatment
polymyxins | tetrecyclines
167
how old is the TB bacterium?
70000 years old
168
what are risk factors for TB infection?
``` crowding HIV infection malnutrition diabetes alcohol use active smoking indoor pollution ```
169
how is TB transmitted?
through aerosols not through contact or food
170
what is the infection dose of TB?
very low: 3-10 bacilli
171
what are the 4 stages of TB infection?
exposure latent - has TB but no symtoms active - signs and symptoms reactivation of latent infections
172
what are the characteristics of the M. tuberculosis pathogen
``` gram positive long rods waxy outer membrane highly aerobic intracellular slow replication ```
173
what is the outer waxy layer of the M. tuberculosis pathogen made of?
mycolic acids - long chain FAs hydrophobic membrane permeability barruer cell wall is key for virulence
174
describe the pathogenic lifestyle of M. tb
bacterium enter lung through aerosols at alveolar surfaces, macrophages are recruited and the bacteria are internalised inside the macrophage, the bacteria replicate and this recruits other immune cells and further lymphocytes arrive at the site of infection and surround infected macrophages (granular maturation) granuloma start to die (granuloma necrosis) and the bacteria start replicating and taking over with extracellular replication transmission via breathing in out to another person
175
How does M.tb survive within the host?
Primarily replicates and survives within macrophages | produces several proteins and enzymes that block macrophage processes to enable survival
176
how does M. tb enter the macrophage?
enters through receptor-mediated endocytosis in a phagosome
177
what happens once the M. tb is inside the macrophage?
blocks maturation of the phagosome prevents phagolysosomal formation and acidification induces cell death in macrophages Mtb then disseminates to infect other macrophages
178
what are the symptoms of active lung TB?
``` cough with sputum and blood chest pains weakenss weight loss fever and night sweats ```
179
what are the symptoms of extrapulmonary TB?
organ-specific | hard to diagnose early
180
how is TB diagnosed?
Mantoux test - positive skin test or blood test only says whether someone has been infected or not chest x ray will show active disease bacterial culture from sputum rapid molecular diagnosis tests -high diagnostic accuracy PCR
181
how is TB treated?
isoniazid rifampicin ethambutol treatment period is 6-9 months some drugs have several side effects
182
is there a TB vaccine?
BCG- Bacille Calmette Guerin vaccine
183
what was the most severe pandemic in history?
spanish flu 500 million infected 50 million deaths
184
is the black death a zoonitic disease?
yes | transmits from animals to humans - bite or direct contact with infected tissues
185
what is the fatality risk for the bubonic plague?
30-60%
186
causes of emergence of pathogens with pandemic potential
``` global travel urbanisation climate change increased animal and human contact health worker shortages ```
187
what is the aim of a pandemic response?
limit spread and contain/slow progression of epidemic ensure prompt and appropriate clinical care to reduce morbidity and mortality identify knowledge gaps and develop tools to prevent disease and improve treatment limit impact in terms of health, economic and social aspects of society
188
what are the stages of an emergency response?
prevention preparedness response recovery continuous process
189
what are the stages of a pandemic?
no known cases - focus on preparing, surveillance a few cases, small clusters - focus on containment, break transmission chains widespread community transmission - suppression and mitigation, reduce transmission
190
strategies for response to COVID-19
containment suppression mitigation
191
what are features of case-based interventions?
testing and contact tracing - detect and isolate cases, monitor close contacts, self isolation
192
what are features of population based interventions
``` face masks social distancing closure of hospitality and entertainment work from home close schools ```
193
what are features of border control measures
travel restrictions | mandatory quarantine
194
what are the stages of vaccine development?
discovery phase 1 - given to a small group of healthy individuals for initial safety data phase 2 - determine safety effectiveness phase 3 - safety and effectiveness dose, side effects RCT regulatory - review and approval phase 4 - surveillance for adverse events, new formulations
195
what is a drug used in covid treatment that was initially a malaria treatment
chloroquine consequently people with malaria who actually needed it suffered
196
what are key features of public health surveillance?
``` ongoing systematic - collect same data - 'like for like' collation - from multiple sample points analysis - using appropriate methods interpretation dissemination ```
197
what are the aims of surveillance?
1. assess public health status 2. evaluate public health programmes 3. inform research 4. define public health priorites
198
what is the surveillance cycle?
1. data collection and collation 2. analysis and interpretation 3. dissemination of information
199
what is indicator surveillance?
specific identity, could be pathogen specific
200
what is event-based surveillance?
big outbreak
201
What is passive surveillance?
being informed about cases
202
What is active surveillance?
searching for cases | -case finding
203
what is sentinal surveillance?
doesn't cover whole populations, only parts but its representitive
204
what is comprehensive surveillance?
every case is identified - should know every measles case for example
205
what is participatory surveillance?
invitation to take part e.g., surveys - TICK SURVEY
206
what is syndromic surveillance?
cough for example
207
Use influenza as an example for surveillance strategy
``` syndromic surveillance sentinal GP surveillance indictor based - hospital admissions or ICU admissions mortality lab reports ```
208
what is the outcome of analysis?
reassurance allow NHS to plan services identification of increased local activity early warning of outbreaks
209
what is the 'person' aspect of descriptive epidemiology?
count sick people define a case aids decision of who should be included in the surveillance system can be graded as suspect, probable, confirmed
210
what is the 'place' aspect of descriptive epidemiology?
map | q
211
what is the 'time' aspect of descriptive epidemiology?
analysis of data by time e.g., daily collection compare data on a day-by-day basis see trends, seasonality, fluctuations monitoring trends over time
212
what are common failures in analysis?
person - failure to take into account population structures e.g., density, age, sex structure place - misclassification in terms of place of reporting time - misclassification in terms of date onset, date of diagnosis, date of reporting failuire to take step by step approach first aand produce approprite reccomendtions following analysis
213
what is the rule for interpreting data?
``` should always treat an increase as real until proven otherwise but consider potential sources of error -changes in testing -delays in reporting -changes in reporting -impact of media reporting -completeness of data ```
214
what is infectious disease modelling used for?
study the mechanisms by which diseases spread, predict future outbreaks and/or evaluate strategies to control/prevent disease spread make comparisons where clinical trials aren't available - alternative courses of action check generalisability of interventions
215
name some common tyes of models
decision tree Markov model patient-level simulation
216
what are decision trees used for?
compare interventions various consequences from 2 courses of action costs vs benefits
217
what are the 3 health states of the markov model
progression free progression dead
218
what is herd immunity?
direct protection experienced by unvaccinated individuals resulting from the presence of immune individuals in a population
219
what must a model reflect?
natural history of the disease
220
should models be complex?
models should be as simple as possible and no simpler
221
what is a stochastic model?
allows the number of models who move through compartments to vary through chance - make assumptions
222
what is a deterministic model?
describes what happens on average in a population- should be similar every time
223
what is the force of infection?
- the rate at which susceptible individuals become infected per unit time - force of infection is the probability per unit time that a susceptible person acquires an infection - incidence of infection can be derived by multiplying the force of infection by the number of susceptible people
224
what is R0?
'average number of secondary infectious persons resulting from one infectious person following introduction into a totally susceptible population' if R0 = 1 the incidence of disease in the population remains the same and doesn't change if R0= >1 the incidence of disease in the population will increase if R0=<1 the incidence of disease in the population will eventually disappear
225
what is Rn
net reproduction number: average number of secondary infectious persons resulting from one infectious person in a given population the higher proportion that are immune the lower the probability the person becomes infected
226
what is opportunity cost?
choices must be made competing uses of limited resources the benefit you give up due to not being able to spend money on more than one thing 1 heart bypass = 10 cateracacr removals = 300 flu vaccines
227
how do you reduce the amount of agent released? | infection control in the workplace
treating cases to reduce the infectious period isolating cases eliminating/reducing environmental reservoirs
228
what is a fomite?
any inanimate object that can carry and spread disease and infectious agents e.g., touch screens, rails, money, door handles
229
what are the 6 steps in a chain of infection?
1. infectious agent 2. reserviour 3. portals of exit 4. mode of transmision 5. portal of entry 6. susceptible host
230
what are common challenges to breaking the chain of infection?
``` high use of antimicrobial agents high prevalence of antimicrobial-resistant organisms high use of invasive devices/procedures patients who are frequently immobile patients who are undernourished ```
231
what is source isolation (standard)
isolation in a side room, usually with en-suite
232
what is protective isolation?
patients who are severely immunocompromised through illness are particularly susceptible to infection and may require specialist protective isolation
233
what is negative pressure isolation?
prevents contaminated air mixing with clean air - ventilation system to outside not in the building.
234
what is strict isolation?
rare infectious diseases designated high level isolation unit negative pressure room
235
what is cohort nursing?
happens when there aren't enough rooms to isolate patients either cohorted with the same organism e.g., MRSA or if they have the same symtoms e.g., diarrhoea should be cared for by designated staff in designated bay or ward
236
how much do facemasks reduce transmission by?
53% (Tara et al, 2021)
237
what is the prevention paradox in relation to face masks?
an intervention that brings moderate benefits to individuals but large population benefits
238
collectivism vs individualism related to face masks
in east asia, face coverings were widely used pre-pandemic (normative practise) could be due to past experience with respiratory virus or a civic mindset (interdependence over independence) or air pollution
239
what is individualism in relation to facemasks?
individualism refers to the dominant values in a society where people are loosely connected to each other and where the expectation is to look after oneself only and immediate family
240
individualism vs collectivism- what is better when it comes to a health crisis?
collectivist values led to specific health-related behaviours that ultimately reduced transmission rate and kept more people alive collectivist cultures responded quicker to health crisis
241
what is the optimism bias?
human brain believes that our chances of experiencing negative events are lower and are chances of experiencing positive events are higher than our peers - illusion of invulnerability can lead to poor decision making with sometimes harmful consequences - not wearing suncream, not wearing seatbelts can be positive - self-esteem, lower stress
242
what is psychological reactance?
unpleasant arousal when an individual is asked to follow orders that they believe infringe on their personal choices and autonomy men are more likely to argue it infringes on their freedom women are more likely to claim its uncomfortable as a reason for non-compliance mask-wearing seen as breach of personal freedom
243
what is haemogenic masculinity?
this is the ideal concept of being a man domiant masculinity can exert a social power and dominance over other masculinities (effeminate, gay, introverted) and women as people are socialised to to value those aspects of men face covers may be seen as a threat to masculinity, symbol of subversivience or weakness - toxic masculinity
244
Who is more susceptible to misinformation?
low health literacy
245
how does anti-intellectualism affect facemask adherence?
there is a generalised distrust of experts and intellectuals people tend to be persuaded by speakers when they perceive them as knowledgeable and if they share a common interest less amenable to expert messages as a result even in a time of crisis individuals who scored higher for anti-intellectualism were significantly less likely to obtain COVID-19 information and guidance
246
describe how conspiracy theories affect face mask-wearing in relation to the social cognition model
this theory predicts behaviour outcome expectations conspiracy theories can diminish pro face cover wearing outcome expectations and therefore reduce uptake of the behaviour
247
describe how conspiracy theories affect face mask-wearing in relation to the theory of planned behavior
conspiracy theories can negatively affect attitudes towards wearing facemasks in people who believe them making them less likely to enact the behaviour some people wearing masks have faced alienation or discrimination which reduces their perceived control which reduces likelihood of behaviour if mask uptake is low its likely to be deemed as a subjective norm which further reduces behaviour likelihood
248
Who invented the vaccine 1796?
Edward Jenner
249
what is a vaccine?
mimic a pathogen and stimulate a protective immune response stimulate immune memory which allows the body to be prepared to fight off infection next time the body is challenged/attacked by a pathogen memory T snd B cells reside in germinal centres, lymphatic system including spleen and bone marrow
250
what is the role of B cells in vaccines and immunity?
b cells are triggered by vaccine > plasma cells > memory B cells
251
what is a prophylactic?
preventative measures e. g., a vaccine they prepare the immune system to defend the body against infection e. g., beta-blockers prevent heart attacks e. g., birth control to prevent pregnancy
252
what is a herd immunity threshold?
the level of immunity required within a population that stops the spread of the virus its pathogen-specific e.g., small pox - 80-85% measles - 93-95%
253
what is the R0 number for SARS-CoV-2?
2-3 | if an infected individual encounters 10 other people , on average, 2 of them will become infected
254
what is the basic composition of a vaccine?
1. a vector or platform - a delivery system e.g., adenoviral vectors 2. antigen or vaccine target - part of the virus or bacteria that produce an immune response (3. sometimes an adjuvant is added that helps mimic the inflammatory effects of infection, producing a better immune response)
255
what are the features of the influenza vaccine?
negative RNA strand virus 8 segments H1 and H3 influenza subtypes, in addition to 2 influenza B lineages circulate in the human population heamagglutinin (HA) is the major surface antigen in influenza.
256
how many deaths and cases of influenza are there each year?
between 200000 to 600000 deaths each year | between 1 to 4 million severe cases per year
257
describe the influenza vaccine components?
trivalent and quadrivalent vaccines consist of one strain of H1N1 influenza A and one strain of H3N2 influenza A as well as one strand of influenza B
258
what is the protectiveness of the flu vaccine?
33% of individuals who receive it get protection reformulated every 3 years
259
describe features of the SARS-CoV-2
positive single stranded virus major antigen is the spike protein genome encodes 16 proteins binds to ACE2 receptor endocytosis is triggered and fusion occurs genome is released in an environ and duplicates zoonotic reserviour
260
what are the methods for creating covid vaccines?
target spike proteins replication-competent vaccines - display spike proteins - expensive, difficult inactivated virus vector vaccines - display spike proteins - expensive, difficult DNA vaccines - plasmid - quick, cheap RNA vaccines - quick and cheap
261
how many deaths does immunisation prevent every year?
2-3 million deaths every year
262
what is vaccine hesitancy?
a delay in acceptance or refusal of vaccination despite the availability of vaccination services - its a continuum range of attitudes towards vaccines
263
what is the 3C's model?
complacency confidence convenience
264
describe the complacency aspect of the 3 C's model in relation to vaccine hesitancy
low health literacy misunderstanding of vaccine importance subscribing to conspiracy theory belief that natural immunity or natural foods are sufficient for infection prevention
265
describe the confidence aspect of the 3 C's model in relation to vaccine hesitancy
scepticism about vaccine effectiveness and true purpose distrust in authorities subscribing to conspiracy theories that vaccine is unsafe/has side effects lower vaccination rates among minority groups due to lower levels of trust/confidence - historical abuse
266
describe the convenience aspect of the 3 C's model in relation to vaccine hesitancy
not being eligible for a vaccine at a particular time point e.g., only certain age groups invited living in a country with limited vaccine availability individuals may be unable to afford cost of vaccination
267
what is omission bias?
tendency to react more strongly to harmful actions than to harmful inactions
268
how do we reduce vaccine hesitancy?
concerns need to be addressed and dealt with empathy 1/3 claimed it was easier if administered by a doctor people need standardised, accurate and informative resources to empower people to make the right choices for themselves
269
what is a fear appeal - vaccination uptake
persuasive messages that attempt to arouse fear by emphasising potential danger research shows that threats or coercion is not always effective at changing attitudes or internal motivation towards a behaviour
270
what is the tri risk model and how is it used to explain vaccination uptake?
1. risk belief and anticipated regret about infectious diseases correlate reliably with whether individuals get vaccinated or not 2. social processes can motivate getting vaccinated - humans are generally influenced by perceived normative behaviour 3. affective risk - worry, fear, anxiety can spur people to get vaccinated
271
what a sort of messages proved successful to promote vaccination?
those that included personal benefit reduced vaccine hesitancy in those that were strongly hesitant those that are strongly hesitant are more likely to feel excluded from wider public for their views so don't respond well to collective benefit messages
272
what is health inequity?
differences in health status or in the distribution of health resources between different population groups arising from the different social conditions in which people are born, grow, live work and age
273
what are the 2 urgent interests in a pandemic in the global community?
1. lifesaving vaccines be created, manufactured and distributed 2. the disease be quickly contained and eliminated worldwide
274
what role do pharmaceutical companies have in vaccine inequity?
they have financial interests - product usually goes to the highest bidde rather than where there is the greatest need disproportionate distribution happens as a result
275
what are the statistics of vaccine distribution globally?
wealthy countries with 14% of the world's population bought 53% of the most promising vaccines - hoarding
276
how many deaths could have been avoided if vaccines were distributed fairly?
61% of deaths if vaccines had been distributed to all countries proportional to the population
277
what is COVAX?
covid 19 vaccine global access facility aimed to contribute to equitable distribution of the covid vaccines worldwide vaccines delivered as soon as available high-income countries, companies and philanthropic organisations would cover the cost for 92 of the poorest countries.
278
what are 6 things we knew about covid but didn't realise we did?
1. we knew covid was coming - good to properly be prepared 2. most people will be okay over time 3. the poor and vulnerable are liable not only to disease but also poor mental health 4. culture matters too, in terms of myths and other beliefs 5. politics goes alongside trust, particularly when being aksed to try something new 6. in challenging times, resources are important for relationships
279
what proportion of people wear masks to protect themselves?
96%
280
what proportion of people get vaccinated to protect themselves?
84%
281
what is a natural product in terms of chemistry/drug development?
a chemical compound that has been made by a living thing secondary metabolite - not strictly essential for organisms survival any product made by a living organisms e.g., plant extracts, honey, bile
282
what is a stigmasterol?
it is used as a precursor for lots of human hormones e.g., ostrogen, progesterones, testossterone used for emergency contraceptives, HRT, breast cancer, hypogonadism
283
what natural product is now used in chemotherapy?
pacific yew tree bark - chemically fractioned and used to kill cancer cells - blocks mitosis
284
what is ethnopharmacology?
study of substances of traditional/folk medicines look at historical medicines instead of trying to discover new ones
285
What makes it difficult to know if promising antibiotics in the lab are transferrable to humans?
bacteria make biofilms so bacteria grow differently in humans than on. a petri dish
286
what is the pathway for testing if drugs are safe?
start with cell lines - cheap & easy but overestimates damage en vivo organ - a collection of structured differentiated cells live animal model - more realistic see systemic effects, very expensive, ethical concerns, licence needed human phase 0 trial - low dose on healthy people
287
what is the 3 rule when it comes to testing?
Reduce Define Replace cows eyes are often used in cosmetic testing, take from slaughter house, animal is already dead
288
how do we isolate the molecules bacteria produce to analyse them?
analytical chemistry separation sciences - chromatography structural characterisation - NMR, Mass spectroscopy
289
what is mortality?
number of deaths
290
what is morbidity?
DALYs | years life lost due to premature mortality and years lived with a disability (YLD)
291
In 2016 how many people were infected with an NTD?
~1 billion
292
how much funding do neglected tropical diseases get annually?
$300million
293
what was the 2012-2020 WHO roadmap for NTDs?
series of goals and strategies vector controls established in 10 endemic countries (dengue) more than 1 million surgical treatments were provided (trachoma)
294
What is the definition of eradication?
permanent reduction to 0 of the worldwide incidence of infection caused by a specific pathogen no risk of reintroduction
295
What is the definition of elimination?
reduction to 0 of the incidence of infection caused by a specific pathogen in a defined geographical area with minimal risk of reintroduction continued action to prevent re-establishment of transmission may be required
296
What is the definition of 'elimination as a public health problem'?
reduction of infection and disease to measurable targets set by the WHO continued action is required to maintain the targets and/or to advance interruption of transmission
297
What is the definition of control?
reduction of disease incidence, prevalence, morbidity, and or mortality to a locally acceptable level continued interventions are required to maintain the reduction
298
what disease is on the verge of eradication with only 54 human cases reported in 2016?
dracunculiasis
299
what are the WHO 2021-2030 targets for NTDs?
aim to free more than 1 billion people who currently require interventions against NTDs and reduce out of pocket expenditure 90% reduction in people requiring NTD interventions 100 countries having eliminated at least one NTD 2 NTDs eradicated
300
what are core strategic interventions for NTDs?
preventative chemotherapy WASH - water sanitation, hygiene veterinary public health case management
301
how many people don't have access to basic drinking water services?
785 million
302
how many people practise open defication?
946 million
303
types of diagnostics for NTDs
need them to be cheap and easy to run - require little training need molecular tests that rely on a biomarker antigen - LFTS antibody - ELISA, rapid lateral flow test (IgM, IgG) Nucleic acid - PCR, LAMP
304
how does a lateral flow test work?
1. Identify a biomarker 2. add biological sample to sample pad 3. the sample flowing through conjugate pad that contains labelled antibodies specific to the antigen 3. antibodies specific to antigen are also adhered to test line 4. if antigen is present is present it is captured by the test line along with the labelled antibodies, visible as a line
305
what is sensitivity in terms of a diagnostic tool?
true positive rate | the proportion of people who ARE positive that TEST positive
306
what is specificity in terms of a diagnostic tool?
true negative rate | the proportion of people who ARE negative that TEST negative
307
what are the features of a good diagnostic tool in terms of specificity?
it depends on the incidence/burden of the disease: | must have higher specificity when the disease incidence is low
308
what are common challenges when it comes to NTDs?
political instability - funding, disruption, migration, refugees climate change - alters vector-borne disease epidemiology and spread antimicrobial and insecticide resistance - expansion of preventative chemotherapy, widespread use of insecticides for vector control zoonosis - animal reserviour
309
What is schistosomiasis?
caused by 6 different species of parasitic worms humans are infected through contaminated water most species live in the mesenteric vein system of humans
310
how is schistosomiasis transmitted and spread?
transmitted through contact with infected water (human = definitive host) the worm lives in the mesenteric vein system female worms lay 200-3000 eggs each day in the blood humans excrete eggs in faeces or urine when contaminated faeces or urine reaches freshwater, the eggs hatch they swim to the snail (intermediate host) of the right species and the parasite migrates through the snail and ultimately sheds larvae they swim to find a new host and reinfect by penetrating the skin
311
how many people are affected by schistosomiasis worldwide?
240 million people | in 2016 there were 24000 deaths and 2.5 million DALYs
312
what is the pathology of schistosomiasis?
initial rash at the site of inoculation Katayama syndrome - acute phase - nocturnal fever, cough, headache, abdominal tenderness, lasts 14-84 days chronic phase - weakness, fatigue, abdominal pain - fibrosis and lesions of organs containing trapped eggs - kidney disfunction - fertility issues associated with - undernutrition - lost years of schooling - growth stunting - exercise intolerance
313
what strategies have the WHO introduced to eliminate schistosomiasis?
``` preventative chemotherapy to break the chain of transmission praziquantel - recommended drug improved sanitation access to potable water access to toilets - stop open defecation sewage treatment snail control - molluscicides vaccines - no current vaccines ```
314
what is the life cycle of dracunculiasis/ guinea worm disease
people become infected when they drink water containing copepods (water fleas containing infective larvae) the copepods are killed by digestive juices of the stomach released larvae move to the small intestine where they penetrate the intestinal wall and migrate to connective tissues of the thorax and abdominal wall blister forms on the skin where the worm will eventually emerge (legs and feet) blister bursts within 24-72 hours when blisters are submerged in water, the worm releases larvae which are ingested by copepods and the lifecycle begins again.
315
what is the epidemiology of dracunculiasis/guinea worm disease
affects poor communities in remote parts of Africa with no safe drinking water transmission has a seasonal pattern -in dry regions, people get infected in rainy season - stagnant surface water -in wet regions peole get infected in dry season - surface water is stagnant most common in 15-45 yr olds - farmers, herders, fetching water greatest risk is if you were infected the year before
316
what is the pathology of dracunculiasis/guinea worm disease?
``` the worm is 2mm wide and 60-100cm long no symptoms first year and then people become ill - fever - rash - nausea - vomiting - diarrhoea ``` wounds often become infected - sepsis - tetanus - abscess rarely lethal disability that occurs during worm removal and recovery prevents people from working, going to school, caring for family for around 8.5 weeks but it can be permanent disability
317
how is dracunculiasis/guinea worm disease managed?
no vaccines or drugs once part of the worm emerges, it;'s pulled a few cm each day by being wound around a stick or gauze process takes weeks
318
what is the dracunculiasis/guinea worm disease eradication programme?
drink only from protected water sources cook fish and aquatic animals well before consuming prevent people with blisters/visible worms etc emerging skin in water distribute basic water filters chemically treat unsafe water only 28 cases reorted in 2018
319
what causes African sleeping sickness?
the Trypanosoma brucei parasite - unicellular and extracellular 2 different sub-species of African trypanosome
320
how is African sleeping disease transmitted?
Tsetse flies
321
what is African sleeping disease?
humans - fatal disease - 1000 cases per year - no vaccine and treatments can be highly toxic animals - called Nagana - major cause of poverty - have to kill livestock
322
what defines the distribution of African sleeping disease?
the vectors - tsetse fly only occurs in 36 sub-Saharan countries these people are most exposed to the fly the disease is in rural populations that are dependent on agriculture, fishing, hunting major disease loci in the DRC
323
how is African sleeping disease controlled?
``` target parasite reservoir in host screening and treatment programmes in humans treatment of domestic cattle eliminating wild animal reservoir better health of population ``` target vector spraying insecticides insecticide-treated fly traps and bed nets blue fly traps
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what are the symptoms and pathology of African sleeping disease?
1. inflammation at bite site 2. early-stage - heamolymphatic stage - enter bloodstream 3. late-stage - encephalitic stage - trypanosomes cross the blood-brain barrier - fatal
325
what is the life cycle of the trypanosome?
vector: tsetse fly host: mammls skin is a major reservoir adipose tissue is also.a major parasite reservoir - upregulating fat metabolic enzymes
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what are the 2 distinct lifestyle stages of trypanosomes in the host?
1. slender - long, proliferate, glucose metabolism via glycolysis, non-tranmissable. differentiate into stumpy form 2. stumpy - short, cell cycle arrested, active mitochondria, preadapated to survival in midgut
327
describe the stumpy form of the trypanosome
this form proliferates at high parasitaemia, they differentiate into stumpy forms this is quorum sensing and is due to secreted parasite factors this limits parasitaemia and preserves the life of the host, enhancing parasite transmission stumpy forms are then transmitted via the tsetse bite
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summarise the trypanosome lifecycle
infect mammals transmitted by tsetse flies differentiate through multiple cell types to complete the lifecycle 1. slender - proliferative form in host 2. stumpy - non proliferative - transmissible form preadapted for tsetse 3. procyclic - establishes tsetse midgut infection 4. metacyclic - non-proliferative form that develops in insect salivary glands that innoculate new host
329
how do trypanosomes evade the immune system?
extracellular parasites SO ARE EXPOSED TO HOST IMMUNE FACTORS VSG - varient surface glycoproteins hydrodynamic flow - endocytosis
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what is antigenic variation?
its the switching of expression sites to evade the immune system trypanosomes have ~20 different VSG loci/expression sites at chromosome telomeres only the expression site is expressed - monoallelic switch to one that hasn't been seen yet
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what is symbiosis?
close biological interaction between 2 different species
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what is mutualism?
symbiotic relationship in which both species benefit
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what is commensalism ?
symbiotic relationship in which one species benefits and the other is not affected
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what is parasitism
a symbiotic relationship in which one species benefits while the other species (host) is harmed.
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what is the causative agent of Leishmaniasis?
Leishmania. spp
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how is Leishmania. spp transmitted?
sandflies
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what is the disease burden of Leishmaniasis?
350 million people live in endemic areas | 12 million infected
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what is visceral leishmaniasis?
viscera = organs fatal if left untreated in over 95% of cases caused by L. infanum and L. donovani
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what are the symptoms of visceral leishmaniasis?
irregular bouts of fever weight loss enlargement of spleen and liver and anameia
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what is cutaneous leishmanisasis?
cutaneous = skin caused by > 20 different species of leishmania most common form not usually fatal causes skin lesions, mainly ulcers usually heals within a few months leaves life long scares and serious disability or stigma
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what is mucocutaneous leishmaniasis?
mucocutaneous = skin and mucous membrane caused by Leishmania braziliensis leads to partial or total destruction of mucous membranes of the nose, mouth or throat
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why is the burden of leishmaniasis likely to increase?
population mobility - migration, movement of non-immune people to areas of high prevalence environmental changes - changes in urbanisation, human incursion into forested areas climate change - changes in temp, rainfall and humidity can have strong effects on vectors - alter distribution and transmission
343
describe the cell biology of leishmania
there are 2 leishmania forms that invade vertebrate immune cells 1. promastigote - inoculated by the sandfly - elongated, flagellated form - powerful swimmer - invades phagocytic immune cells 2. amastigote - formed by promastigote after its first invasion - small, round - immotile flagellum - invades phagocytic immune cells - infects sandfly - found in mamallian bloodstream
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what is a digenetic parasite?
colonises two different species 1. vector: sandflies - phlebotomine 2. host - mammals
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how is leishmaniasis transmitted?
bite of female sandfly regurgitate leishmania parasites into the wound upon biting parasites in promastigote form infect mammalian host 1. promastigote uptake into parasitophorous vacuole 2. differentiation and diversion: differentiation to amastigote 3. amastigote escape and reinfect 4. amastigote replicate inside parasitophosphorous vacuole 5. escape and reinfection
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how do parasites get inside macrophages?
parasites are internalised via conventional phagocytosis parasites bind to phagocytic receptors stimulates phagocytosis pathway and parasite is internalised inside a parasitophorous vacuole parasites subvert the classic pathway nutrients destined for other parts of the cell are diverted to the PV to feed the parasites vesicles carrying parasite damaging factors are less able to fuse with the PV membrane the parasite prevents the macrophage from activating other immune cells that might inhibit the parasite infection
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life in the sandfly vector
sandfly insert mouthparts into skin and produce wound where blood flows into superficial capillaries amastigotes are taken into sandfly midgut leishmania development happens in digestive tract - extracellular
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what happens in the sandfly midgut?
parasites start in the midgut as amastigotes (shortened, immotile flagellum) transform into promastigotes in resposne to temp and pH drop promastigotes progress through 5 stages 1. colonize midgut 2. nectomad - attached to midgut microvilli 3. leptomonad 4. heptomonad 5. metacyclic
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how do parasites overcome insect defences?
chitinases to break free of matric that surround them resist proteases by secreting inhibitors downregulate protease genes in sandfly insert flagellum between insect gut epithelium microvillli and bind to receptors to prevent them from being expelled secrete peptides that inhibit insect gut peristalsis movements
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Of the 900 + sandfly species, how many can transmit leishmania?
98 - high specificity with ability of parasite to bind to the phosphglycans on the epithelial microvilli
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what is the blocked sandfly phenotype?
Promastigote secretory gel blocks the valve containing many infective parasites the plug forces the valve to remain open and causes a blockage that reduces the inflow of blood this promotes delivery of parasites to the host via regurgitation these flies also feed more often because of feeding being inefficient
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what pharmacologically active compounds are in sandfly saliva?
anticoagulants to prevent clotting vasodilator peptides to promote blood flow -attracts macrophages to bite site -activates macrophages for Leishmania infection
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what 4 different species cause human malaria?
plasmodium falciparum - causes most deaths p. vivax- uncomplicated malaria p. avale - uncomplicated p. malariae - uncomplicated
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what is the geographical distribution of malaria?
94% of cases and deaths were in Africa 41% of worlds population live in areas where malaria is transmitted
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what is the pathology of malaria?
characterised by bouts of fever occurring every other day - up to 40.5 degrees linked to synchronised release and invasion of parasites from RBCs
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what are the 2 types of malaria?
uncomplicated - fever (hot and cold cycles), parasitaemia, anaemia complicated - severe anameia, cerebral malaria (coma and death), caused by P. falciparum
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what causes complicated malaria?
infected cells undergo changes in their cell surface RBCs change shape and develop knobs these knobs contain the parasite protein pfEMP1
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what is the impact of pfEMP1 in malaria development?
pfEMP1 on the infected RBC knobs are sticky - can bind to at least 7 different receptors on the endothelium. also, stick to non-infected erythrocytes forming a rosette. infected RBCs are less flexible which makes it difficult to pass through microvasculature - sequestration and causes vascular occlusion which blocks blood flow - this enables the parasite to avoid spleen dependant killing mechanisms
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how does sequestration causes cerebral malaria?
sequestration of parasite in the brain | blocked capillaries in the brian become swollen and congested leading to haemorrhage, coma and then death
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why is plasmodium a digenic organism?
requires 2 hosts to complete lifecycle vector - anopheles spp - mosquito host - human
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what happens when mosquitoes feed from blood vessels?
during feeding they continuously release saliva the saliva contains anti-clotting chemicals and bioactive compounds infected mosquito saliva contains plasmodium parasites sporozoites (spores) pass through the mosquito proboscis into the dermis upon biting once inside the parasites move around until they reach a blood vessel - gliding motility
362
describe the liver stage of invasion of malaria
sporozoites reach the liver within 1 hour post-infection they attach to Kupffer cells and then cross into the liver they then transmigrate through several hepatocytes and then switch to invasion mode and start to replicate inside parisotophophorus vesicles (PV) eventually develops into thousands of merozoites by membrane invagination these rupture PV membrane and enter host cytoplasm eventually merozoites reach the lungs to infect RBCs
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SPOROZOITES IN LIVER & MEROZOITES OUT OF LIVER
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What happens to merozoites in the RBCs?
they enter the RBCs inside a PV using invasion machinery merozoite undergoes multip,e nuclear divisions to produce a schizont this matures via division, releasing merozoites from the PV 16-32 merozoites egress from RBCs to infect new RBCs MEROZOITES IN RBCs & MERZOITES OUT OF RBCs
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merozoites are non-transmissible so how is malaria transmitted to mosquitos?
they have to differentiate into transmissible gametocytes inside the RBCs - microgametocytes - analogous to sperm - macrogametocytes - analogous to egg needs to be a balance between keeping the infection going and transmitting the infection MEROZOITES IN RBCs & GAMETOCYTES OUT
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summary of parasite lifecycle in the mammal (malaria)
1. sporozoites inoculated into the dermis by the bite of an infected mosquito 2. pass into blood vessels and taken into the liver by blood flow 3. at the liver, they pass through several liver cells before they colonise a hepatocyte PV 4. sporozoite then develop into thousands of merozoites 5. merozoites re-enter the blood system inside vesicles m(merosomes) and replicate inside erythrocytes 6. merozoites are not transmissible 7. they must differentiate to gametocytes to transmit to mosquitoes
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what happens in the mosquito midgut?
fertilisation male gametocytes undergo flagellation male gametes fertilise female gametes to form a DIPLOID zygote zygotes differentiate into male ookinetes these become oocysts and lodge in basal lamina of midgut epithelium
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how dooes the parasite move from midgut to the salivary glands?
oocysts grow in size and produce 1000s of sporozoites by meiosis> haploid upon maturation, sporozoites are released into open heamolymph circulation of mosquito moves to salivary glands and into salivary gland cavity enter secretory duct and are transmitted upon biting
369
give a summary of the lifecycle of plasmodium
1. merozoite - human RBCs 2. gametocytes - micro = male, macro = female) - transit to mosquito 3. gametes - insect midgut 4. ookinete - moquito midgut 5. oocyst - midgut epithelium 6. sporozoite - mosquito salivary glands, then human skin, then liver via blood system \
370
what is the relationship between haemoglobin and sickle cell anaemia?
geographical overlap between sickle cell anaemia and malaria suggests the selective advantage of sickle cell heterozygotes against p. falciparum infection parasites are less able to grow inside sickled erythrocytes growth arrest
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what drug is used to treat malaria?
chloroquine resistance has emerged so rarely used in complicated malaria used in uncomplicated P. vivax
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what is the mechanism of action for chloroquine drug?
parasites metabolise haemoglobin to hemozoin crystals inside their food vacuoles haemoglobin is metabolised to hemozoin via heme which is toxic to the parasite but doesn't normally accumulate chloroquine becomes pronated in the low pH of the food vacuole and accumulates it prevents the breakdown of hemozoin causing toxic heme accumulation which lyses and kills the parasite
373
what are the features of a 21st-century containment lab?
control of aerosols - no work on an open bench waste inactivation - autoclave negative pressure - stops contaminated air from escaping when doors are opened ability to fumigate - deals with spillages - formaldehyde effluent disinfection - everything put down the drain goes through disinfectant system
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what are the classifications of biological agents based on?
severity of disease risk to workers likelihood of community transmission availability of vaccines or effective treatments
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what are features of a hazard level 1 agent?
unlikely to cause human disease e.g., E.coli lab strain
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what are features of a hazard level 2 agent?
can cause human disease maybe hazardous to employees unlikely to spread to the community usually effective prophylaxis is available e.g., influenza
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what are features of a hazard level 3 agent?
can cause severe human disease may be a serious hazard to employees can spread to community usually effective prophylaxis, treatment available e.g., SARS-CoV-2 TB P. falcuparum
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what are features of a hazard level 4 agent?
causes severe human disease a serious hazard to employees likely to spread to the community usually no effective prophylaxis/treatment is available e.g., Ebola,
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how are aerosols managed?
``` the following techniques generate aerosols: centrifugation sonication - break open cells flow cytometry and cell sorting vigorous pipetting action ``` control by use of MSCs (microbiological safety cabinets)
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what are class 2 MSCs?
sample protection operator protection used up to containment level 3 the most common mode of primary containment only effective if the airflow is undisturbed keep lab doors shut keep grilles clear
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what are class 1 MSCs?
high-level operator production not designed to provide sample protection can be used to containment level 3 less sensitive to disruption than class 2
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what are class 3 MSCs?
maximum operator protection sample protection environment protection can be used at containment level 4
383
what is genetic modification?
introduction of foreign DNA into any organism by a method that doesn't occur naturally - the transformation of plasmids into bacteria - transfection/duction of tissue culture cells - mutagenesis - growth, storage, transport of any resulting organism GMO regulations require a risk assessment
384
what are the general principles when it comes to controlling GI infections?
``` stool sample collection identify a source mode of transmission - helps define control measures diarrhoea - enteric precautions risk groups exclusion -48 hour microbiological clearance - negative stool samples ```
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what are the methods of GI infection transmission?
faeco-oral foodborne environmental airborne
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what are the 6 F's - vehicles of GI infection?
``` food flies fingers faeces fluid formites ```
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what are primary prevention methods of GI infections?
food-safety - farm to fork water quality - filter and disinfection public awareness - open farms, summer BBQs foreign travel - vaccines, drinking bottled water, not eating from street vendors
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what are the 4 high-risk groups for GI infections?
doubtful personal hygiene children aged 5 and under food handlers clinical, social care or nursery staff
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what are the rules surrounding GI infections and stool samples?
with suspected cases, a stool sample is required and is sent into the lab so pathogen can be identified negative samples required before returning to work
390
what is the most common cause of Gi infection?
campylobacter - most common cause of gastroenteritis undercooked meats, contaminated water, animal contact generally mild illness low chance of person to person spread
391
what is an antimicrobial agent?
antimicrobials are used to prevent and treat infections caused by microorganisms in humans, animals and plants includes antifungals, antiparasitic, antivirals, antibiotics
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how do antibiotics work?
the challenge is to avoid damage to human cells the target is the cell wall, cell membrane, folate/protein synthesis, DNA/RNA synthesis
393
how to antivirals work?
challenge: viruses reproduce in human cells mechanisms of action: - inhibiting attachment/entry of virus to host cell - inhibiting reproduction e.g., acyclovir - inhibiting virus leaving cell
394
how to antifungals work?
mechanisms of action - impact on cell membrane via ergosterol - act via cell wall
395
how do microbes develop resistance?
natural process genetic diversity natural selection of resistance genes making them more abundant in the bacteria population 1. this spreads to other humans/animals 2. spreads to other bacteria - sharing resistance via horizontal gene transfer
396
what role do antibiotics have in microbe resistance?
antibiotics kill off competing bacteria which aids the process as the strain of resistant bacteria is the one that's being transmitted to other people
397
what are some examples of resistance mechanisms?
efflux- antibiotics are pumped out of the cell target modification immunity/bypass - stop antibiotic accessing target enzymes - stop antibiotics from functioning
398
what is minimum inhibitory concentration?
the minimum concentration of antibiotics in which bacteria can grow e.g., culture with a strip that has gradated levels of antibacterial agent in
399
what is the minimum bactericidal concentration (MBC)?
minimum conc of antibiotics that kills it add liquid cultures mixed with increasing concentration of antibiotics to a series of cultures
400
what are the drivers of AMR?
misuse and overuse inappropriate prescribing inappropriately used - not finishing the course use for growth production/prophylaxis in animals low-quality drugs
401
what are some issues with drug development?
lack of new drugs in pipeline market failure/wrong incentives more opportunity to recoup profit from drugs for chronic conditions, high cost cancer drugs from an AMR perspective - want drugs to be used as infrequently as possible infectious diseases are not seen as a priority as they are not very profitable
402
what are some consequences of antimicrobial resistance?
harder to treat > higher fatality risk longer treatment> multi-drug resistant TB more expensive treatment length of stay increased use of drugs that were previously avoided due to side effects cost to individuals when unwell for longer
403
how many deaths were associated with bacterial AMR?
4.95 million
404
how many deaths were attributable to bacterial AMR?
1.7million
405
what is the one health approach?
an approach that recognises the interconnections between humans, animals and environmental health cant just take the human perspective
406
what is the most common STI in the UK?
chlamydia
407
what are the symptoms of chlamydia?
``` pain when urinating discharge bleeding during/after sex, between periods or heavy periods lower abdominal pain testicular pain ```
408
what are some complications of chlamydia?
Causes Pelvic inflammatory disease - can lead to infertility, miscarriage, ectopic pregnancy in males, it can lead to orchitis, prostates and rarely reactive arthritis, meningitis and infertility
409
what is the second most common STI in the UK?
Genital warts
410
What does the blood test offered to pregnant women looking for in terms of infectious diseases?
Hepatitis A HIV Syphilis needs to be done as early as possible to reduce vertical transmission
411
what is the success of the HPV vaccine?
reduced HPV infection in 86% of young women | and pre-cancerous cervical disease by 71%
412
when was relationship and sex education made statutory in all schools?
september 2020