Infection Flashcards

(418 cards)

0
Q

In what ways can you get an infection?

A

Directly from a source
Indirectly from a source via an intermediary (vector) or the environment (water, air, food, surfaces)
Directly from animals
From the patient themselves (microbiota= commensals)

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1
Q

What is infection?

A

The invasion of a hosts tissues by micro organisms causing disease

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2
Q

What are microbiotae/ commensals?

A

Microorganisms carried on skin and mucosal surfaces that are normally harmless or even beneficial, but can be harmful and cause disease if and when they are transferred to other sites

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3
Q

What are some methods of horizontal transmission?

A

Contact- direct, indirect and vectors

Inhalation- droplets (influenza) and aerosols (TB, chickenpox - spreads vastly)

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4
Q

What are some methods of vertical transmission?

A

Mother to child

Before or at birth

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5
Q

What 5 stages are involved in how microorganisms cause disease?

A
Exposure
Adherence 
Invasion
Multiplication
Dissemination
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6
Q

What are some virulence factors of infection?

A

Exotoxins - cytolytic, AB toxins, super antigens, enzymes

Endotoxins

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7
Q

What are virulence factors?

A

Molecules expressed and secreted by pathogens that enable them to achieve Exposure, Adherence, Invasion, Multiplication and Dissemination and cause host cellular damage

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8
Q

What are the 4 P determinants of disease?

A

Pathogen (virulence factors, inoculum size (dose), antimicrobial resistance (antibiotics))
Patient (site of infection, comorbidities)
Practice
Place

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9
Q

What precedent would you follow to find out whether a patient has an infection?

A

History
Examination
Investigation

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10
Q

What history would you take of a patient you’re suspecting of having an infection?

A

Symptoms
- focal (specific), systemic (not specific)
- severity
- duration
Potential exposures
- e.g. Travel- where? what? who with? animals involved?

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11
Q

What main examination would you do on a patient you’re suspecting of having an infection?

A

Check for organ dysfunctions

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12
Q

What investigations would you do on a patient you’re suspecting of having an infection?

A

Specific
- looking at microorganisms directly
Supportive
- full blood count - neutrophils and lymphocytes
- C Reactive Protein
- blood chemistry- liver and kidney function tests
- imaging - x ray, ultrasound, magnetic resonance imaging (MRI)
- histopathology
—-> virology - antigen detection, antibody detection, detecting viral nucleic acid (DNA/RNA)
—-> bacteriology - specimen types (swabs, fluids, tissues), MC&S microscopy (bacterial and patient cells), culture, antibiotic susceptibility

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13
Q

What’s a pathogen?

A

Disease causing microorganism

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14
Q

Briefly describe viruses

A

10^-8 - 10^-7 m
Spikes- for attaching to specific surfaces
Envelopes
Protein coats (protects and organises)
Can be antigens - immune response promoted, facilitates viral entry into cell

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15
Q

What is the Baltimore classification of viruses?

A
I dsDNA 
II ssDNA 
III dsRNA 
IV (+)ssRNA , (-)ssRNA 
V (-)ssRNA 
VI ssRNA- RT DNA RNA dsDNA
VII ds-DNA-RT 

–> mRNA

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16
Q

Briefly describe bacteria

A

10^-6 - 10^-5m
Pilii, cell wall, capsule, cytoplasm, plasma membrane, plasmid, nucleoid, ribosomes, flagellum

Coccus- (circular) Stapphy (clusters) Strepty (chains)
Spirillus- (spiral)
Bacillus- rods

Gram positive
Gram negative

Aerobes (obligate)
Anaerobes (obligate)
*exception of obligate anaerobe - require O2 free environment for survival –> spores - survive at high temperature, pressure etc, don’t cause disease as spores

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17
Q

What is the pathogenesis of bacteria?

A

Virulence factors
- host entry (polysaccharide capsule)
- adherence to host cells (Pilii, fimbriae)
- invasiveness (collagenases)
- iron sequestration
Toxins- exo (diphtheria) endo (lipopolysaccharide)

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18
Q

Briefly describe fungi

A
Yeasts (single celled) 
- Candida albicans (thrush) 
- cryptococcosis neoformans (trees)
- pneumocystis jiroveci
Moulds (multicellular) 
- aspergillus species (bread) 
- dermatophytes (ringworm, athletes foot)
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19
Q

Briefly describe parasites

A
Protozoa (single celled) 
- gardia lamblia (diarrhoea) 
- cryptosporidium parvum (diarrhoea) 
- plasmodium falciparum (malaria) 
- trypansosoma cruzi 
Helminths (worms, multicellular)
- roundworms (enterobius vermicularis)
- tapeworms (taenia saginata)
- flukes (schistosoma mansoni)
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20
Q

What does Coccus mean?

A

Round bacteria

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21
Q

What does stapphy- mean?

A

Clusters of cocci bacteria

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22
Q

What does strepto- mean?

A

Chains of cocci bacteria

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23
Q

What does spirillus mean?

A

Spiral bacteria

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24
What does bacillus mean?
Rod shaped bacteria
25
What is an example of a single-stranded, non-enveloped DNA virus?
Parvovirus 19
26
What are some examples of double-stranded, non-enveloped DNA viruses?
Adenovirus BK virus Human papilloma virus JC virus
27
What are some examples of double-stranded, enveloped DNA viruses?
Herpes virus Hepatitis B Molluscum contagiosum
28
What are some examples of single-stranded, positive, icosahedral, non-enveloped RNA viruses?
``` Coxsackievirus Echovirus Enterovirus Hepatitis A & E Norovirus ```
29
What are some examples of single-stranded, positive, icosahedral or helical, enveloped RNA viruses?
``` HIV Hepatitis C Rubella virus Encephalitis viruses Yellow fever virus West Nile virus ```
30
What are some examples of single-stranded, negative, helical, enveloped RNA viruses?
Ebola, Lassa, Marburg Influenza, Parainfluenza Respiratory syncytial virus (RSV)
31
What is an example of a double-stranded, icosahedral, non-enveloped RNA virus?
Rotavirus
32
Describe parvovirus
``` Single stranded Non enveloped DNA virus Child hood rash Slap cheek syndrome ```
33
Describe adenovirus
``` Double stranded Non enveloped DNA virus Respiratory Common cold Pneumonia ```
34
Describe BK virus
``` Double stranded Non enveloped DNA virus Polyomavirus Immunosuppressed Asymptomatic ```
35
Describe human papilloma virus
``` Double stranded Non enveloped DNA virus Keratinocytes, mucous membranes Benign papillomas/cancers, warts STDs ```
36
Describe JC Virus
``` Double stranded Non enveloped DNA virus Polyoma virus Immunosuppression ```
37
Describe herpes virus
``` Double stranded Enveloped DNA virus STD Hepstein Barr ```
38
Describe Hepatitis B
``` Double stranded Enveloped DNA virus Liver Flu like symptoms Unprotected sex Sharing needles ```
39
Describe molluscum contagiosum
``` Double stranded Enveloped DNA virus Small firm raised papules on skin Not painful but itchy Highly contagious- skin to skin ```
40
Describe coxsackievirus
``` Single stranded Positive Icosahedral Non enveloped Enterovirus Digestive tract Unwashed hands and contaminated surfacesFlu symptoms Red blisters Haemorrhagic conjunctivitis ```
41
Describe echovirus
``` Single stranded Positive Icosahedral Non enveloped GI tract Liver failure Myocarditis ```
42
Describe Enterovirus
``` Single stranded Positive Icosahedral Non enveloped Genus ```
43
Describe Hepatitis A & E
``` Single stranded Positive Icosahedral Non enveloped Virus found in stool Liver E in particular - pets/eating meat ```
44
Describe norovirus
``` Single stranded Positive Icosahedral Non enveloped High temp, stomach cramps, headache, aching limbs, dehydration, vomiting, diarrhoea Very contagious ```
45
Describe HIV
``` Single stranded Positive Icosahedral of helical Enveloped Lentivirus (AIDS) Affects helper T cells (CD4+) ```
46
Describe hepatitis C
``` Single stranded Positive Icosahedral of helical Enveloped Liver Conc in blood Blood to blood contact ```
47
Describe rubella virus
``` Single stranded Positive Icosahedral of helical Enveloped First week of pregnancy German/ 3 day measles ```
48
Describe encephalitis viruses
Single stranded Positive Icosahedral of helical Enveloped (Japanese, St. Louis, tick borne, Venezuelan, equine) Inflammation of brain Most commonly caused by herpes simplex virus
49
Describe Yellow fever virus
``` Single stranded Positive Icosahedral of helical Enveloped Fevers, chills, loss of appetitie nausea, muscle pain, headache Bite of female mosquito Vaccine exists Flavivirus genus ```
50
Describe West Nile fever
``` Single stranded Positive Icosahedral of helical Enveloped Flavivirus genus Mosquito Africa--> NY --> USA No vaccine ```
51
Describe Ebola, Lassa, Marburg
``` Single stranded Negative Helical Enveloped Vomiting Diarrhoea Rash Deceased liver and kidney function Fruit bats ```
52
Describe influenza, parainfluenza viruses
``` Single stranded Negative Helical Enveloped Flu symptoms ```
53
Describe respiratory syncytial virus (RSV)
``` Single stranded Negative Helical Enveloped Lower respiratory tract infections ```
54
Describe rotavirus
``` Double stranded Icosahedral Non enveloped Severe diarrhoea among infants Stools- virus passes out ```
55
What are some examples of gram positive cocci bacteria?
``` Staph aureus Coagulate -ve staph Alpha haemolytic streptococci Beta haemolytic streptococci (inc. strep pyogenes) Streptococcus pneumoniae Enterococcus faecalis ```
56
What are some examples of gram negative cocci bacteria?
Neisseria meningitidis Neisseria gonorrhoea Mortadella cattarhalis Acinetobacter baumannii
57
What are some examples of gram positive bacilli bacteria?
Listeria monocytogenes Bacillus anthracis Bacillus cereus
58
What are some examples of gram negative bacilli bacteria?
``` Escherichia coli Klebsiella pneumoniae Proteus species Salmonella typhi Pseudomonas aeruginosa Haemophilus influenzae ```
59
What are the main constituents of the infection model?
``` Pathogen Patient Mechanism of infection Infection Management Outcome ```
60
Expand on Pathogens in the infection model
Virus Bacterium (prokaryotic) Fungus - yeast, mould (eukaryotic) Parasites - protozoa, helminthology (worm) (eukaryotic)
61
Expand on the patient in the infection model
Person - age, gender, physiological state, pathological state, social factors Time - calander time, relative time Place - current, recent
62
Expand on the mechanism of infection in the infection model
``` Contiguous spread (direct) Inoculation Haematogenous Ingestion Inhalation Vector Vertical transmission ```
63
Expand on the infection in the infection model
Attachment --> toxin production --> host damage Attachment --> interaction with host defences --> host damage Attachment --> interaction with host defences --> inflammation --> host damage
64
Expand on management in the infection model
History Examinations Investigations Treatment - Supportive - symptom relief, physiological restoration - Specific - antimicrobials, surgery- drainage, debridement, dead space removal Infection prevention - hospital and community - prevent infection transmission to - other patients, staff and contacts
65
Expand on the outcome of the infection model
Spectrum of Cured to Death with disability and chronic infection being intermediates
66
How are antimicrobials classified?
Antibacterial agents Antifungal agents Antiviral agents Antiprotozoal agents
67
How are antibacterials classified?
``` Bactericidal/ bacteriostatic Spectrum- broad vs narrow Target site (mechanism of action) Chemical structure (antibacterial class) ```
68
What does bactericidal mean?
Antibiotic kills organism completely
69
What does bacteriostatic mean?
Antibiotic inhibits the organism but it can come back
70
What is the relevance of 'classes of drugs'?
Groups together drugs with the same basic function and mechanism of action
71
What are the ideal features of antimicrobials?
``` Selectively toxic Few adverse effects Reach site of infection Oral/ IV formulation Long half life (infrequent dosing) No interference with other drugs ```
72
What are the 4 mechanisms of action of antibacterials?
``` Those that affect: Cell wall synthesis Cell membrane function Protein synthesis Nucleic acid synthesis ```
73
What antibacterials affect cell wall synthesis?
B-lactams (penicillin, cephalosporins) | Glycopeptides (vancomycin)
74
What antibacterials affect cell membrane function?
Polymixins (colistin)
75
What antibacterials affect protein synthesis?
Tetracyclines Aminoglycosides (gentamicin) Macrolides (erythromycins)
76
What antibacterials affect nucleic acid synthesis?
Quinolones (ciprofloxalin, trimethoprim, rifampcin)
77
How do B-lactams work to affect cell wall synthesis?
Cross linkage between peptidoglycan - gives cell wall rigidity Achieved by penicillin binding protein Penicillin gets in and blocks penicillin binding protein so protein can no longer bind to chains of amino acids- no cross linkage
78
How do Glycopeptides work to affect cell wall synthesis?
Sits on peptidoglycan chains and stops penicillin binding protein from binding (acts at an earlier stage than B- lactams)
79
What is the most common mechanism of action of antibacterials?
Interupting cell wall synthesis
80
What is the rarest mechanism of action of antibacterials?
Interrupting cell membrane function
81
In what three ways can organisms become resistant to antibacterials?
Drug inactivating enzymes- B-lactamases, aminoglycoside enzymes Altered target- target enzyme has lowered affinity for antibacterials e.g. resistance to meticillin, macrolides and trimethoprim Altered uptake- reduced ability of antibiotic to get close to bacteria; decreased permeability (e.g. B-lactams) or increased efflux (e.g. Tetracyclines)
82
What is the genetic basis of antibiotic resistance?
Chromosomal gene mutation- bacteria undergo spontaneous gene mutation conferring resistance; when exposed to antibiotics, bacterial cell with resistance survives and multiplies Horizontal gene transfer- plasmid to plasmid or plasmid to chromosome; genetic material moves from one organism to another by conjugation, transduction and transformation
83
In what two ways can you measure antibiotic activity?
Disc testing- impregnate antibody into paper filter disc and observe bacterial growth- organism won't grow where there is sufficient antibiotic to inhibit its growth Minimum inhibitory concentration- more mathematical, lots of test tubes with a range of antibiotic concentrations and the same concentration of organism- organism growth is monitored
84
What are the 4 types of B-lactams?
Penicillins Cephalosporins Carbapenems Monobactams
85
What is the mechanism of action of B-lactams?
Affect cell wall synthesis
86
Benzylpenicillin
B-lactam, penicillin Affect cell wall synthesis Mainly active against streptococci
87
Penicillin V
B-lactam, penicillin Affect cell wall synthesis Mainly active against streptococci
88
Amoxicillin
B-lactam, penicillin Affect cell wall synthesis Mainly active against streptococci Also active against gram negatives
89
Flucoxacillin
B-lactam, penicillin Affect cell wall synthesis Active against staphylococci and streptococci
90
Coamoxiclav
B-lactam, penicillin Affect cell wall synthesis Active against staphylococci, streptococci, anaerobes and Gram negatives
91
Tazocin
B-lactam, penicillin Affect cell wall synthesis Active against staphylococci, streptococci, anaerobes, and High activity against gram negatives including pseudomonas
92
Describe cephalosporins
B-lactam,Cephalosporin (Generations with high gram negative and low gram positive activity; broad spectrum but no anaerobe activity: concern over association with C. difficile)
93
Cefalexin
1st generation cephalosporin, B-lactam
94
Cefuroxime
2nd generation cephalosporin, B-lactam
95
Cefotaxime
3rd generation cephalosporin, B-lactam
96
Ceftriaxone
3rd generation cephalosporin, B-lactam Blindness/ meningitis Good activity in CSF
97
Ceftazidime
3rd generation cephalosporin, B-lactam
98
Meropenem/ imipenem
Carbapenem, B-lactam Very broad spectrum (including anaerobes) Active against most(not all) gram negatives Generally safe in penicillin allergy, other than anaphylaxis
99
Aztreonam
Monobactam, B-lactam
100
What is the main mechanism of action of Glycopeptides?
Affect Cell wall synthesis
101
Vancomycin
Glycopeptides Affects cell wall synthesis Active against most Gram positive (not gram negative) Some enterococci resistant (VRE) Resistance in staphs is rare Not absorbed (oral for C.difficile only) Therapeutic drug monitoring (TDM) required as there is a narrow therapeutic window - give enough, not too much, toxicity
102
Teiccplanin
Similar activity to vancomycin, but much easier to administer Glycopeptides Affects cell wall synthesis Active against most Gram positive (not gram negative) Some enterococci resistant (VRE) Resistance in staphs is rare Not absorbed (oral for C.difficile only) Therapeutic drug monitoring (TDM) required as there is a narrow therapeutic window - give enough, not too much, toxicity
103
What is the main mechanism of action of tetracyclines?
Affecting protein synthesis
104
Tetracycline and doxycycline
Similar, broad spectrum Both oral only Specific use in penicillin allergy usually from gram positive Active in atypical pathogens in pneumonia Active against chlamidya and some Protozoa Shouldn't be given to children younger than 12 years
105
What is the main mechanism of action of aminoglycosides?
Affecting protein synthesis
106
Gentamicin
Aminoglycosides Most common agent Profound activity against gram negative Good activity in blood and urine Potentially nephrotoxic/ototoxic Therapeutic drug monitoring (TDM) required- toxicity to kidney Generally reserved for sever gram negative sepsis
107
What is the main mechanism of action of macrolides?
Affecting protein synthesis
108
Erythromycin and clanthromycin
Macrolides Affects protein synthesis Well distributed including intracellular penetration Alternative to penicillin for mild gram positive infections Also active against atypical respiratory pathogens
109
What is the main mechanism of action of Quinolones?
Affects nucleic acid synthesis
110
Ciprofloxacin
``` Quinolone Affects nucleic acid synthesis Commonest example Inhibits DNA gyrase (coiling of nucleic acid) Very active against gram negatives Also active against atypical pathogens Increasing resistance and risk of CDI ```
111
Trimethoprim and sulphonamides
Inhibitors of frolic acid synthesis Trimethoprim used alone in UK for UTIs When combined with sulphamethoxazole- cotrimoxazole, used to treat PCP (pneumocystitis pneumonia) , has activity against MRSA
112
What are two types of antifungals?
Azoles | Polyenes
113
How do Azoles work?
Antifungal Active against yeasts, and or moulds Inhibit cell membrane synthesis
114
Fluconazole
``` Antifungal Inhibits cell membrane synthesis Used to treat candida Hra, vori, posaconazol Also active against aspergillus ```
115
How do polyenes work?
Antifungals | Inhibit cell membrane function
116
Nystatin and amphotericin
Antifungals Inhibit cell membrane function Nystatin for topical treatment of candida Amphotericin for IV treatment of systemic fungal infections (e.g. Aspergillus)
117
What are two common antivirals?
Aciclovir | Oseltamivir (tamiflu)
118
Aciclovir
Antiviral When phosphorylates inhibits viral DNA polymerase Herpes simplex - genital herpes, encephalitis Varicella zoster - chicken pox and shingles
119
Oseltamivir (Tamiflu)
Antifungal Inhibits viral neuraminidase Influenza A & B
120
Metronidazole
``` Antibacterial and antiprotozoal agent Active against anaerobic bacteria Also active against Protozoa - amoebae (dysentery and systemic) - giardia (diarrhoea) - trichomonas (vaginitis) ```
121
Look at infection model for acute sepsis in the emergency model
Neisseria Meningitidis
122
Define the immune system
Cells and organs that contribute to immune defences against infections and non infectious conditions (harmless substances)
123
Define infectious disease
When the pathogen succeeds in evading and / or overwhelming the hosts immune defences
124
What are the four broad stages of an immune response?
Pathogen recognition - cell surface and soluble receptors Containing / eliminating the infection - killing and clearance mechanisms Regulating itself - minimum damage to host (resolution) Remembering pathogens - preventing disease from recurring
125
What are the two types of immunity?
Innate | Adaptive
126
What are the 4 first lines of defence in innate immunity?
Physical barriers Physiological barriers Chemical barriers Biological barrier
127
What are the physical barriers of the first line of defence of innate immunity?
Skin (SA 1-2m^2) Mucous membrane (mouth, resp tract, GI tract, urinary tract) Bronchial cilia
128
What are the physiological barriers of the first line of defence of innate immunity?
Diarrhoea- food poisoning, allergies Vomiting- food poisoning, hepatitis, meningitis Coughing- pneumonia Sneezing- sinusitis
129
What are the chemical barriers of the first line of defence of innate immunity?
Low pH - skin(5.5) stomach(1-3) vagina(4.4) Antimicrobial molecules -IgA (tears, saliva)- binds specifically to microorganisms and prevents it from attaching to mucous membrane -Lysozyme (sebum, perspiration, urine) -Mucous (mucous membrane) -Beta defensins (epithelium) -Gastric acid and Pepsin
130
What are the biological barriers of the first line of defence of innate immunity?
Normal flora - non pathological microbes - strategic locations- nasopharynx, mouth/throat, skin, GI tracts, vagina, (lactobacillus spp) - absent in internal organs Benefits - compete with pathogens for attachement sites and resources, produce antimicrobials chemicals, synthesise vitamins (K, B12 and others)
131
What are some normal flora found on skin?
``` Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenes Candida albicans Clostridium perfringens ```
132
What are some normal flora found in the nasopharynx?
Streptococcus pneumoniae Neisseria meningitidis Haemophilius species
133
What are some clinical problems associated with normal flora?
-->Normal flora can be displaced from its normal location to a sterile location -breaching skin integrity (skin loss, burns; surgery; injection drug users; IV lines) -fecal oral route (food borne infection) -fecal perineal urethral route (UTI) -poor dental hygiene/ dental work (dental extraction, gingivitis, flossing) (common cause of harmless bacteraemia) Serious infection in high risk patients -asplenic/hyposplenic -damaged prosthetic valves -previous infective endocarditis -antibiotic prophylaxis - -> Normal flora overgrows and becomes pathogenic when host becomes immunosuppressed - diabetes, AIDS, malignant diseases, chemotherapy (neutrophils) - -> When normal flora is depleted by antibiotics - intestine --> severe colitis (clostridium difficile) - vagina --> thrush (Candida albicans)
134
What are the second lines of defence of innate immunity?
Phagocytes | Chemicals
135
How are phagocytes involved in the second line of defence in innate immunity?
Phagocyte-microbe interaction - RECOGNITION - -microbial structures: Pathogen Associated Molecular Patterns (PAMPs) - carbohydrates, lipids, proteins, nucleic acid - -phagocytes: Pathogen Recognition Receptors - Toll like receptors - -opsonisation of microbes: coating proteins called opsonins that bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes - ENGULFMENT - DEGRADATION OF INFECTIOUS MICROBES - -phagocyte intracellular killing mechanisms - --O2 dependent - ROS via NADPH oxidase - --O2 independent - lysozyme, lactoferrin/transferrin, cationic proteins, proteolytic and hydrolytic enzymes
136
PAMP- lipopolysaccharide (LPS) G- | PRR?
PRR- TLR4
137
PAMP- lipoproteins and lipopeptides G- | PRR?
PRR- TLR2
138
PAMP- peptidoglycan G+ | PRR?
PRR- TLR2
139
PAMP- lipoteichoic acid G+ | PRR?
PRR- TLR4
140
PAMP- lipoarabinomannan and mannose rich glycans (Mycobacterium) PRR?
PRR- TLR2
141
PAMP- flagellin (bacterial flagella) | PRR?
PRR- TLR5
142
Describe opsonins and when they are required
Complement proteins- C3b C4b Antibodies- IgM, IgG Acute phase proteins - CRP, mannose binding pectin (MBL) Essential in clearing encapsulated bacteria - neisseria meningitidis - streptococcus pneumoniae - haemophiliis influenzae b
143
How are chemicals involved in the second line of defence in innate immunity?
Complement system- 20 serum proteins, most important C1-C9 - 2 activating pathways (actually 3) - - alternative pathway - initiated by cell surface microbial constituents - - MBL pathway - initiated when MBL binds to mannose containing residues of proteins found on Salmonella spp Candida albicans Cytokines - phagocytosis - chemo attraction, phagocyte activation, inflammation - antimicrobials actions of macrophage derived TNF alpha, IL-1, IL-6 - - liver (opsonins) CRP, MBL (complement activation) - - bone marrow - neutrophil mobilisation - - inflammatory actions - vasodilation, vascular permeability, adhesion molecules, attraction of neutrophils - -hypothalamus- increased body temp
144
What are some examples of major complement proteins and their action?
C3a and C5a - recruitment of phagocytes C3b and C4b - opsonisation of pathogens and inflammation C5 - C9 - killing of pathogens in the Membrane Attack Complex
145
What are some clinical problems associated with the second line of defence in innate immunity?
Infection --> microbial toxins (LPS) --> overreaction of TLR4 receptor --> overreaction of complement (neutrophils, endothelium and monocytes) --> excessive systemic inflammatory response --cytokines shower, coagulopathy, vasodilation, capillary leak (tissue organ perfusion)--> sepsis and multi organ failure Clinical problems start when phagocytosis is reduced - deceased spleen function (asplenic, hyposplenic) - decreased neutrophil number (cancer chemo, certain drugs, leukaemia and lymphoma) - decreased neutrophil function (chronic granulomatous disease, no resp burst) - chediak higashi syndrome (no phagolysosomes formed)
146
What is a hospital acquired infection?
Infections arising as a consequence of providing healthcare So in hospital patients- infection is not present nor incubating at the time of admission -e.g. Onset is at least 48 hours after admission Can also include infections in hospital visitors and health workers
147
What are some common viruses which cause a hospital acquired infection?
Blood borne: Hepatitis B, C, HIV Norovirus Chicken pox Influenza
148
What are some common bacteria which cause a hospital acquired infection?
``` Staphylococcus aureus (inc. MRSA) Clostridium Difficile Escherichia Coli, Klebsiella Pseudomonas pneumoniae, aeruginosa Mycobacterium TB ```
149
What are some common fungi which cause a hospital acquired infection?
Candida albicans | Aspergillus species
150
What is a common parasite which causes a hospital acquired infection?
Malaria plasmodium falciparum
151
What are some patient factors which increase the risk of getting a hospital acquired infection?
``` Extremes of age Obesity/ malnourished Diabetes Cancer Immunosuppression Smoker Surgical patient Emergency admission ```
152
What are some general patient interventions, used to manage a HAIs?
Optimise patients condition- smoking, nutrition, diabetes Antibiotic microbial prophylaxis Skin preparation Hand hygiene
153
What are some specific patient interventions, used to manage a HAIs?
MRSA screens Mupirocin nasal ointment Disinfectant body wash
154
How can you avoid patient to patient transmission of a HAI?
Physical barriers- isolation of infected patients, protection of susceptible patients
155
What are some health worker interventions, used to manage a HAIs?
Healthy- disease free and vaccinated | Good practice- good clinical techniques, hand hygiene, PPE, antimicrobial prescribing
156
What are some environmental interventions, used to manage a HAIs?
Built environment- space, layout, toilets, wash hand basins Appropriate furniture and furnishings Cleaning- disinfectants/ steam cleaning/ H2O2 vapour Medical devices- single use equipment, sterilisation, decontamination Appropriate kitchen and ward facilities, good food hygiene practice Theatres- positive/ negative pressure rooms Immune suppressed patients
157
What are the 4 Ps for infection prevention and control?
Patient - general and specific patient risk factors; interactions with other patients, healthcare workers and visitors Pathogen - virulence factors; ecological interactions- other bacteria and antibiotics/ disinfectants Practice - general and specific activities of healthcare workers, policies and their implementation, organisational structure and engagement, regional and national political initiatives, leadership at all levels from government to the world Place - healthcare environment- fixed and variable features
158
What type of organism is clostridium difficile?
Gram positive anaerobic, bacillus, spore forming bacteria | Example of a hospital acquired infection
159
How does the carriage frequency of clostridium difficile change with length of hospital stay?
Carriage frequency increases with duration of hospital stay
160
Describe the mechanism of infection of clostridium difficile
When gut micro flora are disturbed by antibiotics (cephalosporins and amoxicillin) overgrowth can occur Enterotoxin A and B and binary toxin production causes tissue damage and fluid diarrhoea Some strains which are fluoroquinolone resistance and have evidence of enhanced toxin production are associated with more ever disease and extensive hospital outbreaks
161
What are some clinical features and symptoms of a patient infected with clostridium difficile?
History of previous antibiotic exposure 3/4 loose/ unformed stools per day Possible development of abdominal pain Pseudomembranes seen on sigmoidoscopy on mucosal surface of rectum and sigmoid colon Possible complications of toxic mega colon, bowel perforation and systemic toxicity ---> high mortality
162
What is the treatment pattern for clostridium difficile?
Stop the inciting agent (antibiotic) Treat with metronidazole for 10 days Oral vancomycin and IV metronidazole for severe cases and treatment failures Rapid and strict isolation is essential
163
What investigations would you carry out for clostridium difficile detection?
Detection of toxin or glutamate dehydrogenase (GDH) by enzyme immunoassay (EIA) Detection of toxin genes by nucleic acid amplification test (NAAT) Typing- generally by ribotyping Full blood count U&Es CRP MC&S
164
How can you prevent clostridium difficile infection?
``` Enhanced ward cleaning and attention to hand hygiene is essential Suspect Isolate Gloves and apron Hand hygiene Toxin test ```
165
What are some other clostridium bacteria? And what diseases do they cause?
Botulinum- botulism Perfringens- gas gangrene, food poisoning Tetanii- tetanus
166
What are some common travel infections?
``` Malaria Typhoid Meningococcal septicaemia Dengue Yellow fever ```
167
What is the incubation period for malaria?
1-3 weeks or longer after bite
168
What are the four main species that cause malaria?
Plasmodium falciparum, vivax, ovale and malariae
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What is the vector of malaria?
Female anopheles mosquito
170
What areas of the world is malaria common in?
Africa, Asia, Middle East and South and Central America
171
What is a typical history taken of someone with malaria?
``` Headache Cough Fatigue Malaise Asthsalgia Myalgia Fever chills and sweats which eventually cycle every 3rd/4th day ```
172
What signs of malaria are there (ie. From examinations)?
Other than fever, often few signs (+/- splenomegaly) Cerebral features - coma Respiratory distress (metabolic acidosis, pulmonary oedema)
173
What investigations should be carried out for malaria?
Should be managed by an ID physician Blood smear to detect parasites FBC, U&Es, LFTs, glucose Head CT if CNS symptoms
174
What treatment is available for malaria?
Depends on species causing malaria - plasmodium falciparum- (malignant) quinine, artemisinin - p, vivax, ovale, malaria- (benign) chloroquine +/- primaquine for exo erythrocytic phase)
175
How can one prevent malaria?
Assess risk - knowledge of at risk areas Bite prevention- repellant, adequate clothing, nets, chemo prophylaxis before travel (must include regular returning travellers) Chemoprophylaxis - specific to region, start before and continue after return -doxycycline
176
What is the most common species that causes typhoid (enteric fever)?
Salmonella enterica serorar Typhi/ Paratyphi A, B or C
177
What type of bacteria is Salmonella enterica serorar Typhi/ Paratyphi A, B or C?
Enterobacteriaceae | Aerobic gram negative rods
178
What is the mechanism of infection of Salmonella enterica serorar Typhi/ Paratyphi A, B or C?
Gram negative endotoxin VI antigen Invasion which allows IC growth Fimbriae adhere to epithelium over ideal lymphoid tissue (Peyers patches)--> RE system
179
What are some symptoms and signs of typhoid and paratyphoid?
``` Fever, headache Incubation period- 7-14 days Abdominal discomfort, constipation, dry cough, hepatosplenomegaly, occasionally rash Relative bradycardia Intestinal haemorrhage and perforation Paratyphoid generally milder ```
180
What is usually found upon investigation in someone with typhoid?
Moderate anaemia Relative lymphopenia Raised LFTs (transaminase and bilirubin) Culture- faeces, blood Serology (antibody detection)- no longer used
181
What is the pattern of treatment of typhoid?
Usually treated with ceftriaxone or azithromycin 7-14 days | Resistance may be present against chloramphenicol, ampicillin. Cotrimoxazole, ciprofloxalin
182
How can typhoid be prevented?
Food and water hygiene precautions Typhoid vaccine- high risk travel, lab personnel Vicapsular polysaccharide antigen or live attenuated vaccine Modest protective effect (50-75%)
183
What are some examples of non typhoid all salmonella infections?
Food poisoning salmonellas- salmonella typhimurium, S.enteritidis Symptoms- diarrhoea, fever, vomiting, abdominal pain Generally self limiting but bacteraemia and deep seated infections may occur- excreting organism in diarrhoea
184
What causes brucellosis?
Primary animal pathogen - brucella abortus (cows) - brucella melitensis (goats and sheep) Gram negative cocobacillus - short rounded rods
185
Where is brucellosis most common?
South Europe, Africa, Asia, central and South America
186
What is the mechanism of transmission of brucellosis?
Transmission through skin breaks / GI tract (milk)
187
What are some symptoms/ clinical signs of brucellosis?
Non specific febrile illness (undulant fever) Bone, joint involvement Epididymitis - inflammation/ swollen testes
188
How is brucellosis generally diagnosed?
From blood cultures
189
How is brucellosis commonly treated?
With doxycycline and rifampicin
190
In adaptive immunity, what type of pathogens are considered intracellular microbes? And what MHC class do they correspond to?
Bacteria, viruses, Protozoa Class I MHC (found on all nucleated cells) HLA: A, B, C
191
In adaptive immunity, what type of pathogens are considered extracellular microbes? And what MHC class do they correspond to?
Bacteria, parasites, worms, fungi Class II MHC (found on all dendritic cells. Macrophages, B cells) HLA: DR, DQ, DP
192
In adaptive immunity relating to MHC class I what is the endogenous pathway?
Virus (protein) is taken up and presented on cell surfaces
193
In adaptive immunity relating to MHC class II what is the exogenous pathway?
Bacteria taken up and presents in endocytic vesicle which fuses with lysosomes and destroys bacteria
194
What does the endogenous pathway of adaptive immunity stimulate?
CD8+ T cells - cytotoxic T lymphocytes - process and kill the virus CD4+ T cells (stimulates CD8+ T cells and..) - B cells- antibodies- opsonisation, neutralisaiton, complement activation - macrophages- kill opsonised microbes
195
What does the exogenous pathway of adaptive immunity stimulate?
CD4+ T cells - eosinophils- killing of parasites - B cells- Antibody: IgG4 (opsonisation), IgA (mucosal protection), IgG&IgE (antibody dependent cell toxicity) and IgE (allergies) - mast cells- local inflammation allergies (IgE) - neutrophils- phagocytosis
196
What type of pathogen is streptococcus pneumonia?
``` Gram positive, diplococcus (seen in pairs) Alpha haemolytic (can be variable) ```
197
Describe how streptococcus pneumoniae causes infection
Streptococcus pneumoniae has a polysaccharide capsule that protects it's from phagocytosis There are over 90 highly antigenic capsule sero types and antibodies to specific types are protective Pathogenicity- - pro inflamm cell wall components (e.g. c-polysaccharide) F-antigen - IgA2 protease - pneumolysin, a cytotoxin that stimulates immune responses - adhesins that bind to cell surface carbohydrates (e.g. Choline binding protein A, pneumococcal surface protein A) - tissue damaging enzymes
198
Describe how non invasive pneumococcal infections present
- these occur outside the major organs or the blood and tend to be less serious - bronchitis- infection of bronchi - Otis media - ear infections - sinusitis - infection of sinuses
199
Describe how invasive pneumococcal infections presents
These occur inside the major organs or the blood and tend to be more serious than non invasive ones - Bacteraemia - Septicaemia - Osteomyelitis - Septic arthritis - Pneumonia - Meningitis
200
What investigations should be carried out when suspecting streptococcus pneumoniae infection and what results are expected?
``` Distinctive crackles on chest Blood test Radiography- x ray fluid on lungs Ct scan, MRI scan Blood pressure (low) Lumbar puncture test - sample of CSF Urinary antigen test- urine sample, immunochromatographic assay ```
201
What treatment can be given to someone with a streptococcal pneumonia infection?
Non invasive infection - treating bronchitis, middle ear infection, sinusitis Invasive infection - confusion, resp rate >30, low BP, 65 years old ***
202
How can you prevent streptococcal pneumonia infections?
Conjugate vaccine incorporating 13 capsular stereotypes | Highly immunogenicity in small children
203
What are 11 different causes of (travellers) diarrhoea?
``` Enterotoxigenic escherichia coli Enteroinvasive escherichia coli Campylobacter Salmonella typhi Shigella Vibrio cholera Giardia lamblia Entamoeba histolytica Cryptosporidium parvum Rotavirus Norovirus ```
204
What type of diarrhoea do you get with Enterotoxigenic escherichia coli?
Profuse and watery
205
What type of diarrhoea do you get with Enteroinvasive escherichia coli?
Mild with abdominal cramp
206
What type of diarrhoea do you get with campylobacter?
Bloody
207
What type of diarrhoea do you get with salmonella typhi?
Bloody
208
What type of diarrhoea do you get with shigella?
Bloody
209
What type of diarrhoea do you get with vibrio cholera?
Profuse and secretory
210
What type of diarrhoea do you get with giardia lamblia?
Explosive
211
What type of diarrhoea do you get with entamoeba histolytica?
Bloody
212
What type of diarrhoea do you get with cryptosporidium parvum?
Watery
213
What type of diarrhoea do you get with rotavirus?
Watery mild-severe
214
What type of diarrhoea do you get with Norovirus?
Watery
215
Describe the structure of influenza virus and how this affects it function
``` Enveloped orthomyoxovirus (100nm) Contains a negative single stranded RNA genome divided into 8 segments Structure allows genetic reassortment- so that virus can change its surface antigens ```
216
What fluenza strains can influenza virus take up genetic material from?
Avian and pig
217
How many proteins does influenza virus express? Describe their arrangement.
7 proteins - 3 of which are responsible for RNA transcription Nucleoprotein has 3 antigenic types that designate 3 main virus groups- A , B and c Matrix protein forms a shell under the lipid envelope with haemagglutin and neuraminidase proteins - expressed as 10 nm spikes on the envelope which interact with host cells - virus immunity directed against H and N
218
What are some clinical features of influenza virus?
Incubation period- 1 to 4 days Patients infectious for 3 days - starting from one day before symptoms emerge Headache, myalgia, fever, cough lasts for 3 - 4 days Complications which are more common in elderly people and patients with cardiopulmonary disease, include primary viral and secondary bacterial pneumonia
219
How is influenza diagnosed?
Immunofluorescence inf A, B and C Nucleic acid amplification test (NAAT) - more sensitive and can identify specific stereotype which can indicate whether a patient is infected with a pandemic strain
220
Describe the treatment of influenza
Amantadine | Neuraminidase inhibitors- zanamivir, oseltamivir (tamiflu), vaccination
221
Where is legionella pneumophilia often found?
Found in rivers, lakes, warm springs, domestic water supplies, fountains, air conditioning systems, swimming pools and jacuzzis
222
Between what temperatures does multiplication of legionella pneumophilia occur?
Multiplication occurs at temps between 20 and 40 degree Celsius inside acanthamoeba
223
How is legionella pneumophilia transmitted from person to person?
Transmission via aerosols generated from showers, and air conditioning systems
224
What are some risk factors for legionella pneumophilia infections?
Infection associated with previous lung disease, smoking, high alcohol intake, but previously healthy patients can be infected. Immunocompromised patients in hospitals are vulnerable to infection if the hospital air conditioning is not adequately maintained
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What is the pathogenesis of legionella pneumophilia?
Major outer membrane protein that inhibits acidification of phagolysosomes Macrophage infectivity is required for optimal internalisation Legionella pneumophilia expresses a potent exoprotease
226
What are some clinical features of legionella pneumophilia?
Mild influenza like illness (pontiac) Severe pneumonia (legionnaires disease) which can lead to respiratory failure and high mortality Patients may complain of nausea, vomiting, malaise before lung symptoms become prominent Cough which is unproductive and dyspnoea which is progressive Confusion is common Inappropriate natiuretic hormone production associated with low serum sodium
227
How is legionella pneumophilia infection diagnosed in the lab?
Culture of sputum, bronchoalveolar, lavage fluid Rapid diagnosis by antigen detection in urine Direct Immunofluorescence or nucleic acid amplification test (NAAT) of respiratory specimens Serum antibodies can provide retrospective diagnosis for epidemiological purposes
228
How is infection by legionella pneumophilia treated and prevented?
Effective regimens usually consist of a macrolide antibiotic together with rifampicin Legionellosis- prevented by adequate maintenance of air con systems and by ensuring that hot water supplies are above 45 degrees Celsius to prevent multiplication
229
What type of bacteria is neisseria meningitidis?
Gram negative diplococcus bacteria
230
Describe the structure of neisseria meningitidis and relate this to the function of the structure
Number of sero groups (ABC, W-135) based on polysaccharide capsular antigen (acts as endotoxin) - promotes adherence, prevents phagocytosis, and triggers inflammation by cytokines Evades immune system by preventing phagocytosis Outer membrane acts as an endotoxin
231
How does neisseria meningitidis cause disease?
Endotoxin binds to macrophages Local- Cytokines (tissue necrosis factors and interleukins TNF alpha and IL1) stimulate inflammatory response to promote wound repair and recruit RE system Systemic- Cytokines released into circulation stimulate oath factor macrophages and platelets, goal is for homeostasis to be restored SIRS- homeostasis not restored Also - cytokines promote coagulation and inhibit fibrinolysis causing microvascular thrombosis and organ ischaemia and failure
232
What is SIRS?
Systemic inflammatory response syndrome | Response to non specific insult (trauma, Ischaemia and infection)
233
What is bacteraemia?
Presence of bacteria in blood with or without clinical features
234
What is septicaemia?
Generalised clinical term related to generalised sepsis
235
What is sepsis?
Systemic response to infection- SIRS + documented/ presumed infection
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What is severe sepsis?
SIRS + organ dysfunction / hypoperfusion --> hypotension/ decreased urine output
237
What is septic shock?
Severe sepsis + persistently low BP despite administration of IV fluids
238
How can SIRS be diagnosed?
``` 2 or more of : Temp- 38 degrees Celsius H/R > 90/min R/R >20/ min WBC 12x10^9/L. ```
239
What are some common symptoms of an infection caused by neisseria meningitidis?
Abdominal pain, fever, nausea, weakness, muscle aches, eye pain on exposure to light, pale, cool extremities, widespread purpuric rash
240
What investigations are required for diagnosis of neisseria meningitidis?
``` FBC U&Es EDTA bottle for PCR Blood sugar Liver function test C Reactive Protein Clotting studies Blood gases ```
241
What 3 investigations would confirm the diagnosis with neisseria meningitidis?
Blood culture PCR of blood Lumbar puncture- culture of CSF (only after checking contraindications- glucose and protein elimination in biochem M&C) PCR of CSF (appearance- turbidity and colour, microscopy - WBCs and RBCs, gram stain- PCR referral)
242
How would you treat neisseria meningitidis?
Sepsis 6 within 1 hour 1) give high flow O2 2) take blood cultures and other cultures 3) administer empirical antibiotics (IV) 4) measure serum lactate 5) start IV fluid resuscitation 6) commence accurate urine output measurement Antibiotics : ceftriaxone
243
How would you prevent infection by neisseria meningitidis?
Vaccination- meningococcal vaccines conjugate, achy vaccine- immunocompromised patients and travel protection, serogroup B vaccine, Antibiotic prophylaxis- close contact to infected individuals
244
What are some life threatening complications cause by infection with neisseria meningitidis?
``` Irreversible hypotension Respiratory failure Acute kidney injury (renal failure) Raised IC pressure Ischaemic necrosis of digits, hands and feet ```
245
What type of bacteria is escherichia coli?
Gram negative, anaerobic, rod shaped bacterium Commonly found in lower intestine of warm blooded organisms (commensal) Strains vary in fimbriae - giving the consequential disease and mechanism of infection differences
246
Describe the 5 main strains of E. coli.
Enterotoxigenic E. coli - produce LT and ST toxins that act on the enteric yet to stimulate fluid secretion- diarrhoea Enteroaggregative E. coli - secrete plasma encoded toxin, a serine protease that binds alpha ford in and causes disruption of actin cytoskeleton - strains express ST toxins and haemolysin like toxins - chronic diarrhoea Enteropathogenic E. coli- colonise epithelial cell lining of small intestin and inject effector proteins that causes efface net of microvilli and intimate adherence Enterohaemorrhagic E. coli- strains produce a veto toxin (in vitro) - Haemorrhagic diarrhoea, complicated by haemolysis and acute renal failure (commensal in cattle - transmitted via hygiene failure) E. coli in ureter- express mannose binding fimbriae - associated with lower UTIs and cystitis
247
How is E. coli transmitted?
Eatubg/ drinking food contaminated with faeces Meat (infected during processing) - if not heated above 71 degrees celsius Milk and dairy products and raw fruit and veg (which could have come in contact with faeces)
248
What are some symptoms of E. coli infections?
Bloody diarrhoea, stomach cramps, nausea and vomiting, dehydration, some are Asymptomatic, blood, kidney problems Fever, weakness, bruising, passing only small amounts of urine
249
What investigations are used to diagnose a E. coli infection?
Stool sample, M,C&S, microbiological investigation (blood, and or mucus in stool or immunocompromised patient) FBC Renal function Urea and electrolytes
250
How is E. coli treated?
Most cases- home care and plenty of fluids IV fluids if hospitalised Antibiotics
251
How is E. coli prevented?
Washing hands Washing fruit and veg properly Avoiding cross contamination Using a meat thermometer and cooking meat at proper temp
252
What type of virus is Norovirus?
Single stranded, positive, icosahedral, non enveloped, RNACalcivirus- can cause outbreaks of acute diarrhoea and vomiting in hospitals, care homes, cruise ships and other confined communities Divided into 5 genogroups
253
How is Norovirus transmitted?
Faecal oral route | Aerosols
254
How long is the incubation period for Norovirus?
Symptoms develop after a short incubation period of 24-48 hours
255
Where does Norovirus replication occur? What is the consequence of this?
Virus replication occurs in the mucosal epithelium of the small intestine which results in broadening and flattening of villi and hyperplasia of crypt cells
256
What are the main symptoms of Norovirus infections?
Self limiting acute diarrhoeal illness | Can be present with sudden onset projective vomiting and explosive diarrhoea
257
How can Norovirus be diagnosed?
NAAT | Sequencing is required for epidemiological purposes and to monitor design of future NAAT detection assays
258
How is Norovirus transmission prevented?
Isolation Ward closure Good hand washing techniques
259
What type of bacteria is staphylococcus aureus?
Gram positive clusters of cocci
260
Where is staphylococcus aureus found commensally?
A symptomatic carriage found on 40% of healthy people In nose, skin, axilla or perineum- important in. Healthcare workers especially if they carry an invasive or resistant strain (MRSA)
261
What are the 5 main potential pathogenicity determinants of staphylococcus aureus?
``` Coagulase Adhesion molecules Lytic enzymes Protein toxins Biofilm formation ```
262
What is the activity and effect of coagulase in the pathogenicity of staphylococcus aureus?
Coagulase converts fibrinogen to fibrin and may be involved in forming a protective Barrier
263
What is the activity and effect of adhesion molecules in the pathogenicity of staphylococcus aureus?
Adhesion molecules bing fibronectin and assist with adherence
264
What is the activity and effect of lytic enzymes in the pathogenicity of staphylococcus aureus?
Lytic enzymes such as lipase breakdown the host tissue
265
What is the activity and effect of protein toxins in the pathogenicity of staphylococcus aureus?
Protein toxins such as panton valentine leucocidin (pvl), the toxic shock syndrome toxin (tsst), enterotoxins cause shock and toxicity
266
What is the activity and effect of biofilm formation in the pathogenicity of staphylococcus aureus?
Biofilm formation causes slower growth in extracellular matrix and is difficult to treat with antibiotics- adheres to plastics
267
What is the clinical importance of staphylococcus aureus infection?
Primary skin infections- impetigo- person to person Secondary skin infections- associated with eczema, surgical wounds, intravenous devices, burns Pneumonia- rare but may follow influenza and progress rapidly with cavity formation Endocarditis- rapid and destructive, associated with intravenous drug misuse or colonisation of IV devices Osteomyelitis Septic arthritis
268
Describe the antibiotic resistance of staphylococcus aureus
It was initially susceptible to penicillin but strains that produce B lactamases soon predominated so methicillin and related (flucoxacillin) agents were introduced and replaced penicillin Methicillin resistant S.Aureas (MRSA) emerged- resistance caused by presence of mecA gene - codes for a penicillin binding protein that binds the drug less well. Glycopeptides such as vancomycin or teicoplanin started to be required for these strains Intermediate or hetero resistance to Glycopeptides emerged as an increasing issue and fully Glycopeptide resistant strains (GRSA) have now emerged, resistance being mediated from vanA and vanB genes acquired from enterococci
269
How is staphylococcus aureus treated?
Penicillin if susceptible Flucoxacillin if penicillin resistant Vancomycin or teicoplanin if MR Contril measures are needed in hospitals
270
How is staphylococcus aureus infection prevented and controlled?
Isolation of MRSA and GRSA | Topical mupirocin and chlorhexidune to eradicate carriage
271
How is staph Aureas spread from individual to individual?
Spreads by airborne transmission and hands of healthcare workers
272
How is staph aureus infection investigated and diagnosed?
Blood, U&Es Grows readily on most lab media- selective medium contents high salt to which staph aureus is relatively tolerant Phenotypic identification depends on demonstrating coagulase, catalase enzymes and typical cluster of grapes morphology on gram stain Typing by molecular means can support interventions to control outbreaks
273
What genus is HIV from?
Lentivirus
274
Describe the structural composition of HIV
``` Spherical Enveloped Diploid ss +RNA virus 80-100nm in diameter Non segmented Linear ```
275
How does HIV cause disease?
Retrovirus- uses reverse transcriptase to produce a DNA copy from viral RNA that is incorporated into the host nucleus to become the template for further viral RNA 3 genes are required for viral replication- gag, pol and env 2 types of HIV that are pathogenic to humans- HIV1 (most common around world) and HIV2 (largely confined to W Africa, appears less virulent)
276
How is HIV transmitted from person to person?
Sexually By blood and body fluids From mother to child
277
What is the pathogenesis of HIV?
Viral RNA is transcribed to ssDNA and integrates into host genome Antigenic variation is rapid Virus principally infects cells with a CD4+ receptors- (T Cells and macrophages) Viral replication results in progressive T cell depletion and diminished cell mediated immunity Lacking T cells means that B cell function is also reduced Damage to neural cells stimulates cytokines release - neurological damage Clinical signs mostly caused by secondary infections which occur because CD4+ is decreased and cell mediated immunity is non functional
278
What are the clinical features of HIV?
50-70% of patients have an acute syndrome occurring 2-6weeks after acquisition of HIV --> rash, fever and lymphadenopathy Only about 25% of these patients have symptoms severe enough to have to seek medical attention CD4+ count declines and if untreated reaches a point ( AIDS Non specific symptoms- fever, malaise, arthralgias, headache, sore throat, with lymphadenopathy Early invasion of nervous system - meningitis, encephalitis, peripheral neuropathy, myclopathy
279
In HIV infection, what secondary infections commonly occur?
Bacteria- MTB, mycobacterium intracellulare, Salmonella, streptococcus pneumoniae Protozoa- toxoplasma Gondi, cryptosporidium parvum Fungi- candida sp, cryptococcus neoformans Virus- varicella zoster
280
What's the lab diagnosis for HIV?
Virus can be cultured from circulating mononuclear cells Genome detected by PCR and p24 antigen detected prior to seroconversion (where body makes and antibody to a virus) ELISA is used for antibody screening tests Confirmation either by western blot or line immunoassay
281
What is the treatment for HIV infection?
Several classes of antiretrovirals HAART- night a ruche anti retroviral therapy -Nucleoside reverse transcriptase inhibitors (NRTI's) -Non NRTI's -Protease inhibitors -Fusion inhibitors -Integrase inhibitors -Co receptor/ entry inhibitors -Zinc finger inhibitors (Prevent transmission, maintain virus at less than 50 copies, prevent emergence of resistance, restore immunological function)
282
How is HIV infection prevented?
Avoidance of partners who have a high risk factor and unprotected intercourse Screening of blood products Health education and free needle exchange programme for IV drug users Antigenic diversity has frustrated vaccine development Antiretroviral prophylaxis for infected needle stick injury Mother to child- c section
283
Describe hepatitis b
Hepednavirus Enveloped Contains partially double stranded DNA encoding surface antigen (HBcAg) pre core protein (HBeAg) a large active polymerase protein and a transactivator protein
284
How does hepatitis b virus replicate? Using what enzyme?
Replicates through reverse transcriptase
285
How is hepatitis b transmitted?
Parenteral, congenital/ vertical and sexual routes
286
What is the incubation period for hep b?
2-6months
287
What are some clinical features of hep b?
Congenital infection carries high risk of 10% patients develop chronic hepatitis complicated by cirrhosis or hcc Fulminant diseases carries a 1-2% mortality Acute hepatitis of variable severity developes insidiously Fever malaise jaundice Liver failure, liver cirrhosis, hcc
288
How is hepatitis b diagnosed?
Immunoassay so for HBsAg HBeAg and HBcAg (and associated antibodies) enable diagnosis of acute infection and previous exposure Viral load measured by NAAT and sequencing for resistance mutations allows monitoring for therapy and directs drug choice
289
What treatment is available for hep b infections?
Pegylated alpha interferon Lamitudine, adefovir, entecavir, tenofovir, telbinudine and clerudine - antiviral efficacy Emtricitabine and valtorcitabine are nearing clinical introduction Therapy should be considered in chronic infection as responders have reduced risk of liver damage and liver cancer in the long term HBeAg seroconversion often seen as a success of treatment
290
How can hepatitis b be prevented?
Those at high risk should be immunised with recombinant HBV vaccine- HBsAg based, 3 doses at 0,1,6 months or 0,12,12 months, 95% effective Vaccine and specific immunoglobulin should be administered to neonates of infected mother to reduce transmission Post exposure prophylaxis- (HBsAg) positive source, newborns from HBsAg positive mothers, needle stick injury for HCW's without protection Blood donations must be effectively screened Needle exchange programmes for drug misusers and sexual health education schemes can help to reduce transmission
291
What two surfaces are commensal bacteria found on?
Skin- epithelia, hair, nails | Mucosal surfaces- conjunctival, gastrointestinal, respiratory, genitourinary
292
What viruses are normally found on the skin?
Papilloma | Herpes simplex
293
What bacteria are normally found on the skin?
G+ve staphylococcus aureus, coagulative negative staphylococci, corynebacterium G -ve enterobacteriaceae
294
What fungi are normally found on the skin?
Yeasts | Dermatophytes
295
What parasites are normally found on the skin?
Mites
296
What pathogens are normally found in the vagina?
Lactobacilli | Yeasts
297
What pathogens are normally found in the urethra?
Enterobacteriaceae Lactobacilli Streptococci Enterococci
298
What pathogens are normally found in the intestine?
Eubacterium Lactobacillus Coliform Clostridium
299
What pathogens are normally found in the stomach?
Helicobacter Streptococci Staphylococci
300
What pathogens are normally found in the mouth?
Viridans streptococci
301
What pathogens are normally found in the nasopharynx?
Neisseria meningitidis Streptococci pneumoniae Haemophilius influenzae
302
What pathogens are normally found in the nares?
Staphylococcus aureus
303
What pathogens are normally found in the eye?
Coagulase negative staphylococci Saprophytic neisseria Viridans group streptococci
304
How do people get infections?
Microbiota- commensals; microorganisms carried on skin and mucosal surfaces; normally harmless or even beneficial, transfer to other sites can be harmful Invasion- e.g. Streptococcus pyogenes pharyngitis Migration- e.g. E. coli urinary tract Innoculation- e.g. Coagulase negative staphylococcus prosthetic joint infection Haematogenous- e.g. Viridans streptococcus endocarditis
305
What are some external natural surface infections?
``` Cellulitis Pharyngitis Conjunctivitis Gastroenteritis UTI Pneumonia ```
306
What are some internal natural surface infections?
Endovascular- endocarditis, vasculitis Septic arthritis Osteomyelitis Empyema
307
What can prosthetic surface infections develop on?
``` Intravascular lines Peritoneal dialysis catheters Prosthetic joints Cardiac valves Pacing wires Endovascular grafts Ventriculooeritoneal shunts ```
308
What bacteria can cause prosthetic valve endocarditis less than a year after operation?
Coagulase negative staphylococci
309
What bacteriae (5) can cause prosthetic valve endocarditis more than a year after operation?
``` Viridans streptococci Enterococcus faecalis Staphylococcus aureus HACEK group Candida ```
310
What are the two main organisms that cause prosthetic joint infection and cardiac pacing wire endocarditis?
Coagulase negative staphylococci | Staphylococcus aureus
311
What are the four broad stages in pathogenesis of an infection at a surface?
Adherence to host cell or prosthetic surfaces (pili, fimbriae) Biofilm formation Invasion and multiplication Host response- pyogenic (neutrophils --> pus) or granulomatous (fibroblasts, lymphocytes, macrophages --> nodular inflammatory lesions)
312
How does a biofilm form in infections at surfaces?
Starvation can induce bacteria to shrink and adopt a spore like state known as ultra-micro bacteria which wait in water soil rock or tissue until conditions are suitable for active growth Active bacteria can attach to almost any surface – changes in gene expression transform swimmers to stickers within minutes Attached bacteria multiply and encase colonies with a slimy matrix Nutrients defuse into the matrix Close proximity of cells in the matrix facilitates exchange of molecular signals that regulate behaviour Although antimicrobials damage outer cell layers – biofilm community is Propelled by shear forces aggregated cells can become detached or roll or ripple along the surface in sheets and remain in their protected biofilm state
313
What is quorum sensing?
Controls- sporulation, biofilm formation, virulence factor secretion 3 principles- signalling molecules (auto inducers), cell surface cytoplasmic receptors, gene expression--> cooperative behaviour and more AI production
314
How are surface infections managed?
Diagnosis- aim is to identify infecting organism and it's antimicrobial susceptibilities (sterilise tissue and reduce bio burden); challenges- adherent organisms and low metabolic state/small colony variants; blood cultures; tissue/prosthetic material senication and culture; antibacterials; remove prosthetic material; surgery (resect infected material) Challenges- low metabolic activity of biofilm microorganisms; poor antibacterial penetration into biofilm
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How do you prevent infection on natural surfaces?
Maintain surface integrity Prevent bacterial surface contamination Remove colonising bacteria
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How do you prevent infection on prosthetic surfaces?
Prevent contamination Inhibit surface colonisation Remove colonising bacteria
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What does hypersensitivity mean?
Antigen specific immune responses that are either inappropriate or excessive and result in harm to host
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Describe the sensitisation and effector phase of a hypersensitive reaction
Sensitisation phase - first encounter with the antigen | Effector phase - clinical pathology upon reexposure to the same antigen
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What are the 4 types of hypersensitivity reactions?
Type I - immediate, allergy, (<30min); environmental non infectious allergens (antigens) Type II - antibody mediated (5-12 hours)- antibodies directed against an antigen on the surface of pathogen Type III - immune complex mediated (3-8 hours)- antibodies directed against soluble antigens on immune complex Type IV - cell mediated (24-48 hours)- T cells and B cells - environmental infectious agents and self antigens
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What is an anaphylaxis?
Most forms of hypersensitivity are non-life threatening. Anaphylaxis however is a severe form of Type I hypersensitivity reaction, triggered by the exposure of a pre-sensitised individual to an allergen, causing systemic mast cell degranulation. This leads to: o Vasodilation o Tissue oedema o Airways obstruction o Fall in blood pressure o Shock Acute anaphylaxis should be treated with intramuscular adrenaline, which promptly reverses the symptoms and signs with an increase in blood pressure and reversal of airways obstruction.
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What is the allergen hypothesis?
Explains why people have allergies
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List some common allergens
House dust mite, cockroaches Animals especially domestic pets- cats and dogs Tree and grass pollens Insect venom such as that contained in wasp and bee stings Medicines - e.g. Penicillin Chemicals such as latex Foods- peanuts, milk, nuts etc.
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What are the main cells involved in hypersensitivity reactions?
Mast cells
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What are the 5 broad mast cell mediators?
``` Enzymes- Toxic mediators- Cytokines Chemokines Lipid mediator ```
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How do enzymes mediate mast cell action?
tryptase, chymase- remodel connective tissue matrix
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How do toxic mediators mediate mast cell action?
histamine, heparin- toxic to parasites, increase vascular permeability cause smooth muscle contraction
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How do cytokines mediate mast cell action?
IL4, IL13 - stimulate and amplify TH2 cell response IL3-IL5 - promote eosinophil production and activation TNF-alpha - promotes inflammation, stimulation of cytokines production by many cell types activates endothelium
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How do chemokines mediate mast cell action?
CCL3 (MIP-1alpha) - attracts monocytes, macrophage and neutrophils
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How do lipid mediators mediate mast cell action?
Leukotrienes- C4, D4, E4 Cause smooth muscle contraction increase vascular permeability, stimulate mucus secretion Platelet activating factors- attracts leukocytes, amplifies production of lipid mediators , activates neutrophils, eosinophils and platelets
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Describe the immune mechanism of a type I hypersensitivity (allergic) reaction
Cross-Linking of Antigen-Specific IgE molecules on surface of mast cells or basophils. The cross-linking leads to the degranulation of the cells and the release of vasoactive substances. Reactions typically occur in minutes and form the basis of most common types of allergies, and represent a component of childhood asthma (HDM etc.).
331
Describe the immune mechanism of a type II hypersensitivity reaction
Type II – Antibody Mediated Hypersensitivity IgG antibodies reacting with antigen present on tissues or on the surface of cells. Once the antibodies have bound with the antigen, they interact with complement or the Fc receptor on phagocytic cells, activating these innate mechanisms leading to the induction of a localised inflammatory response and tissue damage. These reactions may occur very quickly, but may also lead to prolonged activation. Examples include: o Goodpasture’s syndrome • Autoantibodies to basement membrane in the lung and kidney o Haemolytic anaemias / Rhesus disease o Stimulating Ab’s • TSH in Grave’s disease o Blocking Ab’s • Ach R in Myasthenia Gravis • Insulin receptor in diabetes
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Describe the immune mechanism of a type III hypersensitivity reaction
Type III – Immune Complex Mediated Hypersensitivity Deposition of immune complexes, usually IgG antibodies. The immune complexes are deposited in various tissues, where they set up inflammatory reactions similar to Type II reactions (Complement activation, phagocyte Fc receptor). The commonest sites of Type III reactions are the skin, joints and kidney, and so present with rash, arthritis and/or nephritis. Examples include: o Systemic Lupus Erythematosus o Farmer’s lung
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Describe the immune mechanism of a type IV hypersensitivity reaction
Type IV – Delayed Hypersensitivity T helper cells activate macrophages or cytotoxic T cells. ``` Activated macrophages/cytotoxic T cells cause tissue damage. Typically delayed hypersensitivity reactions occur two to three days after exposure to the antigen. Examples include: o External antigens • Tuberculoid Leprosy • Contact dermatitis o Autoimmune • Coeliac disease • Multiple sclerosis ```
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What are three effects of the degranulation?
Increased vascular permeability Vasodilatation Bronchial constriction
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How can an allergy be diagnosed?
Blood, serum levels of mast cell products
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What is the skin prick test for allergies?
Inner arm usually Mast cells in epidermis activated Due to increased vascular permeability and vasodilation - wheal and flare reaction- urticaria Needs a trained personell, risk of anaphylaxis in highly sensitive subjects
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What changes occur in the face during an allergic reaction?
Mast cells in deep dermis are activated | Angio oedema- lips, eyes, tongue, upper respiratory airways (fatal)
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What are some systemic changes in the body as a result of an allergic reaction?
Bloodstream- Anaphylaxis Systemic activation of mast cells Hypoventilation, cardiovascular collapse, generalised urticaria, angio oedema - face and resp tract, wheezing
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What treatment is available for anaphylactic shock?
Epinephrine/ adrenaline (IM)-acts on alpha1, beta 1 and beta 2 receptors Reverses peripheral vasodilation and reduces oedema Reverses airway obstruction/ bronchospasm Increases force of myocardial contraction Inhibits mast cell activation Do not delay treatment- 30 minute window Monitor pulse, BP, EG and oximetry
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How would you diagnose the allergy?
Clinical history- atopy, allergens, seasonality and route of exposure Blood test- serum allergen specific IgE Serum mast cell tryptase, histamine (systemic degranulation) Skin prick tests- range of allergens - wheal and flare reaction (>3mm), no antihistamines Challenge tests: food and drug allergies - slight risk of anaphylaxis in highly sensitive patients
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How would you manage an allergy?
Allergen avoidance / elimination Education- parents recognise symptoms, EPIPEN use and call emergency services Medic alert identification tags Drugs- antihistamines (alternate sedating/ non sedating), corticosteroids (topic/systemic), anti IgE igG (omalizulab), anaphylaxis- give injectable adrenaline 0.5mg Allergen desensitisation - involves administration of increasing doses of allergen extracts over a period of years given to patient by injection/ drops/ tablet under tongue (sublingual) ; 90% effective in patients with bee and wasp venom anaphylaxis; given to patients with increased risk of systemic attacks; specialist hospital based unit with resuscitation equipment
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What is endocarditis?
Heart valves may become infected during transient bacteraemia Congenitally abnormal or damaged valves are at greater risk Bacteria may originate from mouth, urinary tract, intravenous drug misuse or colonised intravascular lines
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What are some causes of native valve and late prosthetic valve endocarditis?
``` Viridans group streptococci Enterococci Other streptococci Staphylococcus aureus Coagulase negative staphylococci Fastidious gram negatives ```
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What are some causes of early prosthetic valve endocarditis?
``` Coagulase negative staphylococci Staphylococcus aureus Viridans group streptococci Enterococci and other streptococci Fungi ```
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What are some causes of culture negative endocarditis?
``` NB. Serological diagnosis Previous antibiotic therapy Chlamydophila pneumoniae/chlamydia psittaci Coxiella brunetti- Q fever Mycoplasma ```
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What are some causes of right sided endocarditis?
Nutritionally deficient strains Staphylococcus aureus Mixed infections Fungi
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What's the pathogenesis of endocarditis?
Damage and roughening of endothelium --> fibrin and platelet deposition --> colonisation of deposit --> bacterial multiplication, further fibrin and platelet deposition, immune activation --> systemic signs of infection! development of vegetation, toxic, embolic and immune complex phenomena
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What are some clinical features of endocarditis?
Malaise, fever, variable heart murmurs, arthralgia Classical stigmata - splinter haemorrhages, oilers nodes, microhaematuria, retinal infarcts, finger clubbing, janeway lesions (only in long standing infection) Later stages- septic emboli may cause a stroke With aggressive organisms staphylococcus aureu, disease progresses rapidly and valves may rupture
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How would you diagnose endocarditis?
Diagnosis is made if there are two major Dulce criteria present, or 1 major and 3 minor Major- blood culture with characteristic organisms; persistently positive blood cultures with any organism; evidence of endocardial involvement demonstrated by echocardiogram; new valvular regurgitation Minor- predisposition, fever (>8C), immunological signs
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What are some complications of endocarditis?
Local progression may lead to aortic root abscess Valve destruction may lead to cardiac decompensation Cerebral / limb infarction ya follow septic embolus Nephritis secondary to immune complex deposition can progress rapidly if sepsis is uncontrolled or if antibiotics with renal toxicity are given without care
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What investigations are involved in the diagnosis of endocarditis?
Echocardiography Transthoracic or grand oesophageal demonstrate vegetations in valves Plain chest x ray - evidence of cardiac failure At least 3 sets of blood cultures an hour apart while fever is present Antibiotic therapy should await blood culture - serum tested for antibodies to Coxiella, bartonella, and chlamidya psittaci
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How would you manage a patient with endocarditis?
Antibiotics - on,y when causative organism is known Based on MIC and MBC of antibiotics If gentamicin is used, concentrations must be monitored closely 2-6 weeks Surgical management
353
Describe the communicable nature of infection
Many (all) infections are transmissible: - From a non human source to a human ( food- E. coli, water- cholera, environment- legionella, animals- rabies) - From person to person directly (influenza, reovirus, neisserria gonorrhoea) or indirectly (mosquitoes- dengue, malaria, cats- cat scratch/ toxoplasmosis, ticks- Lyme disease, spotted fever)
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What are the four global consequences of transmission of an infection?
Endemic disease Outbreak Epidemic Pandemic
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What is an endemic?
The usual background rate
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What is an outbreak?
Two or more places linked in time and place
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What is an epidemic?
A rate of infection greater than the usual background rate
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What is a pandemic?
Very high rate of infections spreading across many regions, countries and continents
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What is the basic reproduction number and how does it relate to infection?
R0 the average number of cases one case generates over the course of its infectious period in an otherwise uninfected, non immune population If R0 > 1 => increase in cases If R0 = 1 => stable number of cases If R0 < 1 => decrease in cases
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What are the important concepts of antimicrobial stewardship?
Appropriate use of antimicrobials Optimal clinical outcomes Minimise toxicity and other adverse events Reduce the cost of healthcare for infections Limit the selection for antimicrobial resistant strains
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What are the main elements of an antimicrobial stewardship programme?
Multidisciplinary team and relationships to other quality/ safety teams Surveillance- process measures (measuring what you do) and outcome measures (measuring results you get as a result of what you do) Interventions- persuasive, restrictive, structural
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What is the infectious dose?
Number of microorganisms required to cause infection | Determines transmissibility
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How does infectious dose vary?
By organism By presentation of microorganism By immunity of potential host
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What interventions can help eradicate a pathogen?
Antibacterials including disinfectants Decontamination Sterilisation
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What interventions can help eradicate a vector?
Eliminate vector breeding sites
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What interventions help to improve the health of the patient?
Nutrition | Medical treatment
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What interventions help the immunity of the patient?
Passive- e.g. Maternal antibody, intravenous immunoglobulin | Active- i.e. Vaccination - herd immunity
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Define herd immunity
Herd immunity is a form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity or been vaccinated
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What interventions help to avoid the pathogen or vector in practice?
Geographic- don't go there Protective clothing/ equipment- long sleeves, trousers against mosquito bites; personal protective equipment in hospitals (PPE) (gowns, gloves, masks) Behavioural- safe sex, safe disposal of sharps, food and drink prep
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What interventions or environmental engineering help with prevention of infection transmission in a place?
Safe water Safe air Good quality housing Well designed healthcare facilities
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What are some good consequences of control of infection?
• Decreased incidence or elimination of disease/organism – Smallpox – Polio – Dracunculiasis
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What are some bad consequences of control of infection?
• Decreased exposure to pathogen --> decreased immune stimulus --> decreased antibody --> increased susceptibles --> outbreak • Later average age of exposure --> increased severity – e.g. polio, hepatitis A, chicken pox, congenital rubella syndrome
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How do chronic diseases affect a patient?
Chronic diseases cause a change in the structure or function of affected tissues/ organs which may have the potential for changing the interaction between the patient and microorganisms This may be subsequently and further affected by changes caused by the altered presence of microorganisms and the consequences of treatment e.g. with antibiotics and steroids
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Describe the basic pathogenesis of Cystic fibrosis
AR, defect in CF transmembrane conductance regulator gene in exocrine glands Range of different mutations Most frequent
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What are some clinical consequences of cystic fibrosis?
Defect in CFTR- defect in Cl- transmembrane transport Mucus becomes dehydrated and thick causing blockage in small ducts / characteristic salty sweat Long colonisation and infection with a procession of different organisms Lung damage, antibacterial and steroid treatment
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What are some pathogens which are likely to cause infection in CF patients?
H. Influenzae Staph Aureus Pseudomonas Aeruginosa, Burkholderia Cepacia Atypical Mycobacteria, Candida albicans, Aspergillus fumigatus
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Why is CF so common?
Heterozygosity provides resistance to cholera, typhoid, TB In vitro interactions between CFTR protein and cholerol toxin, salmonella typhi, IC entry but no in vivo demonstration of benefit
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In COPD what cells primarily cause the chronic inflammatory response to inhaled irritants?
Neutrophils and macrophages
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What bacterial microorganisms can cause infection in a COPD patient?
``` S.Pneumoniae H.influenzae Moraxella catarrhalis Ps. Aeruginosa E.Coli ```
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What viral microorganisms can cause infection in a COPD patient?
``` Respiratory syncytial virus Rhinovirus Parainfluenza virus Human metapneumovirus Coronavirus Adenovirus Influenza A virus ```
381
How does having diabetes affect your immunity and consequently cause infections?
Hyperglycaemia and acidaemia impair- humoral immunity, polymorphonucleanuclear leukocytes and lymphocyte functions Diabetic microvascular and macrovascular disease result in poor tissue perfusion and increased risk of infection Diabetic neuropathy- diminished sensation resulting in areas of skin which become unnoticed
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What ENT infections are common in diabetic patients?
Malignant or necrotising otitis externa - pseudomonas aeruginosa - infection starts in external auditory canal and spreads to adjacent soft tissue, cartilage and bone - patients typically present with severe ear pain and otorrhoea Rhino cerebral mucormycosis - in patients with poorly controlled diabetes - especially diabetic ketoacidosis - mould fungi - organisms colonise nose and paranasal sinuses, spreading to adjacent tissues by invading blood vessels and causing soft tissue necrosis and bony erosion
383
What UTIs are common in diabetic patients?
Neurogenic bladder due to diabetic neuropathy leads to defects in bladder emptying Increased risk of a symptomatic bacteriuria and pyuria, cystitis and upper UTIs Enterobacteriaceae (e.g. E.Coli), Ps Aeuroginosa
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What neurological disorders affecting bladder control are common in diabetics?
CNS diseases- Alzheimers, MS, Parkinson's, Encephalitis, Stroke PNS diseases- nerve damage, due to long term heavy alcohol abuse, long term diabetes, neuropathy, syphilis, herniated disk, spinal canal stenosis, pelvic surgery; vitamin B12 deficiency
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Sensory neuropathy, atherosclerotic valvular disease and hyperglycaemia all predispose patients to an increased risk of infection of what? By what causative microorganisms?
Skin and soft tissue S.Aureus (folliculitis, cellulitis) Group A B haemolytic streptococcus (cellulitis) Poly microbial- including 2 of above- enterobacteriaceae, various anaerobes - diabetic foot ulcers and necrotising fascitis
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What infections are common in patients with Down's syndrome?
Respiratory tract infections (viral and bacterial) More common in young people with DS Due to true immunodeficiency or to other factors- altered mucus secretion/ structure of mouth and airways Otherwise healthy person with DS will probably not suffer more serious infections than siblings and will respond to vaccinations
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How is humoral immunity affected in a patient with Down's syndrome?
Decreased neutrophil and monocyte function (chemotaxis, phagocytosis, oxidative burst) Normal number of neutrophils and monocytes Lower (children) or raised (adults) Ig levels despite normal B cell number Normal or high levels of serum IgA and secretory IgA Lowered specific antibody responses upon immunisation Normal/ raised levels of C3/C4/C5
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How is cellular immunity affected in a patient with Down's syndrome?
Altered distribution of T cell populations (e.g. Low CD4+:CD8+) but normal T cell number Decreased T cell function including response to specific antigens and some mitogens Altered T cell intracellular signalling Abnormal cytokines production Lowering of some/ not all NK functions - increased number of NK cells
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What can pseudomonas aeruginosa infection generally cause?
``` Endocarditis Pneumonia Bacteraemia Meningitis ENT- external otitis Eye infections UTIs GI tract infection Skin and soft tissue infection ```
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What is an immunocompromised host?
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms Qualitative and quantitative defect of one or more components of the immune system
391
How is SPUR used to diagnose immunodeficiencies?
``` Infections suggesting underlying immune deficiency are defined as SPUR and so will be: Severe Persistent Unusual Recurrent ```
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What are immunodeficiencies associated with?
An increase in frequency and severity of infections | Autoimmune deficiencies and malignancy
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What is a primary immunodeficiency?
Single gene disorder (or polygenic) which affects the immune system directly HLA polymorphisms
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What is a secondary immunodeficiency?
Underlying disease or condition affecting immune components | Causing decreased components produced and increased loss and catabolism of immune components
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What are 4 examples of B cell deficiencies?
CVID- inability of B cells to mature into plasma cells IgA deficiency- B cell unable to switch to IgA Bruton's disease- impaired B cell development Hyper IgM syndrome- CD40 ligand on activated T cells
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How would someone with a B cell deficiency present?
Reduced production of IgA --> recurrent upper and lower respiratory tract infections (bronchiectasis); GI complications including infections (Giardia) Arthropathies (including mycoplasma and urea plasma) Increased incidence of AI disease and lymphoma & gastric carcinoma Low IgM and IgG because vaccines don't amount in antibody production
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How would you manage someone with a B cell deficiency?
Prophylactic antibiotics Immunoglobulin replacement therapy ( serum IgG > 8) Management of other infections and respiratory function Avoid unnecessary exposure to radiation
398
What are 4 examples of T cell deficiencies?
Di George syndrome- defect in embryogenesis and incomplete development of thymus gland STEM CELL DEFECT- Severe combined immunodeficiency (SCID - decreased B and T cells)- defect in gamma chain used by many receptors- IL2,4,7,9 DEATH OF DEVELOPING THYMOCYTES - Severe combined immunodeficiency (SCID) - defect in adenosine deaminase (ADA) purine nucleoside phosphorylase (PNP) DEFECTIVE T CELL DEVELOPMENT- Severe combined immunodeficiency (SCID) and Omenns syndrome- defect in genes critical for TCR rearrangement and maturation
399
How would someone with DiGeorges syndrome present?
``` Cardiac abnormalities Abnormal facies Thymic hypoplasia Cleft palate Hypocalcaemia 22- chromosomal abnormality ```
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How would you manage someone with Di George's syndrome?
Neonatal cardiac surgery Supplement to correct hypocalcaemia Immune defect variable (low T cell number) - if lower than 0.4x10^9/L- PCP prophylaxis with antibiotics - bone marrow transplantation (severe forms) Use only X irradiated and CMV (-) blood No live vaccines (BCG, MMR, oral polio)
401
How would someone with SCID present?
``` Failure to thrive Long term Antibiotic therapy Deep skin and abscesses of organs Low lymphocyte count (<4-10 cells /ul) Hugh susceptibility to fungal and viral infections - PCP, VZV, CMV, EBV ```
402
How would you manage someone with SCID?
Short term- no live vaccines, only irradiated, CMV- blood products; aggressive treatment of infections, prevention of new infections Long term- bone marrow/ stem cell transplant, gene therapy
403
What are 4 examples of phagocyte deficiencies?
Periodicity- Cyclic neutropenia Leukocyte adhesion deficiency (LAD)- adhesion to endothelium affected, lack of CD18 protein on phagocytes Chronic granulomatous disease- intracellular killing affected, lack of respiratory burst- NADPH oxidase deficiency Chediak Higashi syndrome- failure of phagolysosome formation
404
How would someone with phagocyte deficiencies present?
Prolonged and recurrent infections - skin and mucous membranes - osteomyelitis - deep abscesses (staph A) - commonly staphylococcal (cat +ve) - invasive aspergillosis - inflammatory problems- (GRANULOMA)
405
How would you manage a patient with phagocyte deficiencies?
``` Prophylactic antibiotics/ Antifungal agent/ immunisation Surgical management Interferon gamma - CGD Steroids- CHD Stem cell transplantation ```
406
What is an example of a complement deficiency?
Hereditary angio oedema C1 inhibitor deficiency C1 inhibitor usually inhibits C1 and bradykinin preventing the complement cascade But in deficiency in HAO there is little/no control over the complement cascaded So you get vasodilation and increased vascular permeability as well as increased phagocytosis etc.
407
How is hereditary angio oedema treated?
C1 inhibitor infusion | Fresh frozen plasma
408
What conditions cause secondary immune deficiencies by decreasing the production of immune components?
``` Malnutrition Infection (HIV) Liver diseases Lymphoproliferative diseases Drug induced neutropenia Splenectomy ```
409
What factors cause drug induced neutropenia?
Drugs- e,g, phenytoin, chloramphenicol, alcohol (abuse) Autoimmune Infections- hep B/C, HIV, CMV, Typhoid Bone marrow infiltration with malignancy Aplastic anaemia Vitamin B12/ Folate/ Iron deficiency Chemotherapy- cytotoxic and immunosuppressants Exposure to chemical agents- benzene, organophosphate Radiotherapy
410
How would you manage drug induced neutropenia?
Neutrophils (< 1 x 10 ^ 9) Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately Assess patients risk of septic complications
411
What may cause someone to have to have their spleen removed?
``` Infarction (sickle cell anaemia) Trauma Autoimmune haemolytic disease Infiltration (tumour) Coeliac disease Congenital ```
412
How would someone present post-splenectomy?
Increased susceptibility to encapsulated bacteria- haemophiliis influenzae, streptococcus pneumoniae, neisseria meningitidis OPSI- (overwhelming post splenectomy infection) - sepsis and meningitis
413
How would you manage someone having had a splenectomy?
Penicillin prophylaxis (life long) Immunisation against encapsulated bacteria (at least 2 weeks before splenectomy if possible) Patient info- medic alert bracelet
414
What are the normal functions of the spleen?
Immune - blood borne pathogens- encapsulated bacteria - antibody production- acute response: IgM production; long term production: IgG production - splenic macrophages - removal of opsonised microbes, removal of immune complexes
415
Which three bacteria are encapsulated and thus dealt with by the spleen?
haemophiliis influenzae, streptococcus pneumoniae, neisseria meningitidis
416
What conditions cause secondary immune deficiencies by increasing the loss/ catabolism of immune components?
Protein losing conditions - nephropathy and enteropathy Burns
417
Which infections are pyogenic? What immune cells deal with them?
Staph aureus and strep pyogenes | Neutrophils