microbiology Flashcards
(347 cards)
1
Q
pathogen
A
organism that causes or is capable of causing disease
2
Q
commensal
A
organism which colonises the host but causes no disease in normal circumstance
3
Q
opportunistic
A
microbe that only causes disease if host defences are compromised
4
Q
pathogenicity
A
the degree to which a given organism is pathogenic
5
Q
asymptomatic carriage
A
when a pathogen is carried harmlessly to a tissue site where it causes no disease
6
Q
bacterial nomenclature
A
consists of genus and species
e.g. staphylococcus (genus) aureus (species)
7
Q
areas that are colonised
A
most mucosal surfaces
digestive tracr, nasal cavity, skin, urethra, vagina
8
Q
sterile areas
A
lungs
gallbladder
kidneys
upper urinary tract
9
Q
bacterial morphology
A
divided into coccus (round) and bacillus (rod)
further divided into gram positive or negative
10
Q
structures in bacteria
A
inner and outer membrane capsule chromosome of circular DNA pili flagella
11
Q
differences between gram positive and negative
A
different cell envelope
negative have 2 membranes and lipopolysaccharides
positive have much more peptidoglycan
12
Q
bacterial environment
A
temp= -800 degrees to +80 degrees pH= 4-9
13
Q
growth of bacteria
A
lag phase
exponential phase
stationary phase- number of viable bacteria decreases
14
Q
endotoxin
A
component of outer membrane of bacteria
15
Q
exotoxin
A
secreted proteins
16
Q
gene mutation
A
base substitution
deletion
insertion
17
Q
gene transfer
A
transformation e.g. via plasmid
transduction e.g. via phage
conjugation e.g. via sex pilus
18
Q
plasmids
A
proteins can be synthesised using plasmid DNA
tend to be spread during bacterial conjugation
19
Q
gram stain steps
A
- apply primary crystal violet (purple)stain to fixed, heated bacteria
- add iodide which binds to stain and fixes it to cell wall
- decolourise with ethanol or acetone
- counter stain with safranin (pink)
- negative lipids interact with decolouriser and lose their other lipopolysaccharides and crystal violet- iodide (CV-I) so appear pink with counterstain
- positive are dehydrated by decolouriser and the cell wall and CV-I are trapped in the multilayered peptidoglycan so are purple
20
Q
gram stain of neisseria gonorrhoea
A
similar appearance to kidney beans with concave sides facing each other
21
Q
staphylococci gram stain
A
appear in clusters
22
Q
catalase test
A
flavoproteins reduce O2 using superoxide dismutase- producing H2O2
2H2O2 -> 2H20 +O2
staph are catalase + but strep aren’t
23
Q
coagulase test
A
distinguishes s.aureus (positive) from other staphylococci (negative)
it activates prothrombin to convert fibrinogen to fibrin
a positive test- clot forms
24
Q
latex test for staph. aureus
A
positive= agglutination occurring
25
haemolysis
ability of a bacteria to breakdown red blood cells in blood agar
requires expression of haemolysin
26
optochin sensitivity
strep. pneumoniae are optochin sensitive
other strep are resistant
27
oxacillin disc
the oxacillin disc tests for penicillin sensitivity
resistant strains should have a MIC performed to penicillin to ascertain level of resistance
28
selective indicator medial for fram negactive bacilli
MacConkey agar
| cysteine lactose electrolyte deficient (CLED) media
29
MacConkey agar
o Bile salts inhibit Gram-positive bacteria and inhibits swarming of a Gram negative
bacterium Proteus spp.
o Crystal violet also inhibits some Gram-positive bacteria
o Neutral red acts as a pH indicator so that bacteria that ferment lactose (Lac+) and
release H+ appear pink or red
o Lactose is available for Lac+ micro-organisms
o Peptone is used by Lac- micro-organisms, resulting in production of NH3 and a rise in pH
30
cysteine lactose electrolyte deficient (CLED) media
o Electrolyte deficient media prevents swarming of Proteus mirbilis
o Bromothymol blue is indictor, lactose ferementation causes blue to yellow change,
decarboxylation of L-cyteine results in blue colour
o Used as media for urinary pathogens
31
lactose fermenter on CLED agar
A simple but important method of classifying members of the Enterobacteriaceae is based
upon lactose fermentation. Classically lactose fermenting organisms are E. coli, Klebsiella, Enterobacter and Citrobacter species.
32
non-lactose fermenter on CLED agar
The non-lactose fermenting organisms usually belong to the genera other than those
mentioned in slide ‘Lactose fermenter on CLED agar’. However, some lactose fermenting organisms, because they are late lactose fermenters, may appear as a non-lactose
fermenter. Late lactose fermenters are recognised by a positive ONPG test.
33
motility
distinguishes bacteria
flagella staining patterns
swarming motility patterns on agar
34
oxidase test
-Tests if micro-organism contains a cytochrome oxidase or indophenol oxidase
-Utilises a redox indicator such as N,N,N’,N’-tetramethyl-p-phenylenediamine (TMPD)
-In oxidised state indicator dark blue or maroon
-Implies organism able to use oxygen as the terminal
electron acceptor
35
3 main types of gram positive bacteria
streptococcus
staphylococcus
corynebacterium
36
coagulase
enzyme produced by bacteria that clots blood plasma
| fibrin clot formation around bacteria protects it from phagocytosis
37
staphylococcus
coagulase +ve or -ve
s.aureus is most important (coag +ve)
coag -ve are important in opportunistic infections
38
staphylococcus habitat
nose
| skin
39
MRSA
```
resistant to:
beta-lactams
genatmicin
erythromycin
tetacycline
```
40
staph. aureus virulence factors
pore forming toxins
proteases
toxic shock syndrome toxin
protein A
41
staph. aureus associated conditions
pyogenic- wound infections, pneumonia, endocarditis
toxic mediated- toxic shock syndrome, food poisoning
coag -ve - infected implants, septicaemia
42
coagulase- negative staphylococci
s. epidermidis
| s. saprophticus
43
s. epidermidis
infections in debilitated, prostheses - opportunistic
main virulence factor is ability to form persistent biofilms
44
s. saprophticus
acute cystitis
haemagglutinin for adhesion
urease
45
streptococci classification
haemolysis
lancefield typing
biochemical properties
46
alpha haemolysis
partial
greening
H2O2 reacts with Hb
e.g. s.intermedius
47
beta haemolysis
complete lysis
haemolysins O and S
e.g. s.pyogenes
48
gamma haemolysis
no lysis
| some s. mutans
49
sero-grouping
method of grouping catalase negative, coagulase negative bacteria based on bacterial carbohydrate cell surface antigens
50
infections caused by S. pyogenes
```
wound infections
tonsillitis
otitis media
impetigo
scarlet fever
```
51
S. pyogenes virulence factors
capsule- hyaluronic acid
M surface protein- encourages complement degradation
enzymes
toxins
52
s. pneumoniae
normally commensal in oropharynx in 30% of people
| causes - pneumonia, otitis media, sinusitis, meningitis
53
s. pneumoniae predisposing factors
impaired mucus trapping
hypogammaglobulinaemia
asplenia
54
s. pneumoniae virulence factors
capsule
inflammatory wall constituents
cytotoxin
55
viridans streptococci
collective name for oral streptococci
alpha or gamma haemolytic
some cause dental abscesses
important in infective endocarditis
56
C. diphtheriae
droplet spread
| can grow in the presence of potassium tellurite
57
C. diphtheriae toxin
inhibits protein synthesis
58
C. diphtheriae prevention
vaccination with toxoid
59
most relevant gram negative bacteria
proteobacteria
chlamydiae
spirochaeta
bacteroidetes
60
proteobacteria
family of enterobacteriacaeae
rods
motile
facultatively anaerobic
61
e. coli infections
```
wounds infections
UTIs
gastroenteritis
travellers diarrhoea
bacteraemia
meningitis
```
62
why are some e.coli strains pathogenic
have additional DNA that causes them to be pathogenic
| several pathovars, many serotypes or strains
63
shigella
closely related to e. coli
four species- dysenteriae, flexneri, boydii, sonnei
severe bloody diarrhoea
64
pathogenesis of shigella
acid- tolerant
person-person or contaminated water and food transmission
65
invasion of shigella
moves form cell to cell in colonic mucosa
| cause damage to mucosa which results in diarrhoea
66
shigella virulence determinant
shiga toxin- causes cell death by blocking protein
67
salmonella
two species= enterica and bongori (rare)
68
salmonella infections
gastroenteritis
enteric fever
bacteraemia
69
salmonella pathogenesis
- ingestion of contaminated food/water
- invades gut epithelium of small intestine
- intestinal secretory response
- does not produce toxins
- enters submucosa
- intracellular survival/replication
70
vibrio cholerae
facultative anaerobe
curved rods with single polar flagellum
cholera= most severe diarrhoeal disease
71
vibrio cholerae pathogenesis
```
faceal-oral route
incubation
voluminous watery stools
no blood, pus or fever
60% mortality
```
72
vibrio cholerae virulence determinants
TCP pili required for colonisation
| cholera toxin
73
pseudomonas aeruginosa
single polar flagellum
opportunistic
antibiotic resistant
74
pseudomonas aeruginosa acute infections
localised- burns, UTI, keratitis
systemic
ICU patients
75
pseudomonas aeruginosa chronic infections
cystic fibrosis patients
76
pseudomonas aeruginosa virulence determinants
twitching motility
| multiple toxins
77
legionella pneumophila
immunocompromised
severe 15-20% mortality
fastidious- charcoal agar
78
legionella pneumophila pathogenesis
modulates trafficking of phagosome
avoids phagosome-lysosome fusion
differentiate to replicative phase
79
bordetella pertussis
whooping cough
short rods- coccobacilli
fastidious
non-invasive
80
bordetella pertussis toxins
pertussis toxin
| adenylate cyclase- haemolysin toxin (increases cAMP)
81
neisseria
non-flagellated diplococci
fastidious
2 species= meningitidis and gonorrhoeae
82
n. meningitidis
```
asymptomatic in nasopharynx of 5-10%
rises to 20-90% during outbreaks
aerosal transmission (person to person)
```
83
n. meningitidis pathogenesis
crosses nasopharyngeal epithelium and enters blood stream
| enters subarachnoid space after crossing blood brain barrier
84
n. meningitidis virulence determinants
capsule is major determinant
85
n. gonorrhoeae
asymptomatic in 30% of females
person-person sexually transmitted
proctitis, gingivitis, pharyngitis
86
n. gonorrhoeae virulence determinants
twitching motility
| non-capsulated
87
campylobacter
spiral rods
unipolar or bipolar flagella
most common cause of food poisoning
88
bacteroides
non-motile rods
strict anaerobes
commensal flora of the large intestine is most abundant (30-40%)
most common cause of anaerobic infections
89
chlamydia
small and non motile
obligate intracellular parasites
many live asymptomatically as endosymbionts
90
growth cycle of chlamydia
2 developmental stages-
elementary bodies= infectious, enter cell through endocytosis, prevent phagolysosome fusion
reticulate bodies= replicative, non-infectious, possess tubular projections
91
life cycle of chlamydia
- entry as elementary bodies
- prevent phagolysosome fusion
- conversion into reticulate body
- multiplication
- convert back to elementary body
- cell lysis and release
92
chlamydia. trachomatis
most common std
can spread to uterus and ovaries
usually asymptomatic
can also cause conjunctivitis- hand to eye
93
Chlamydophila. pneumoniae
respiratory tract
| infects other mammals
94
Chlamydophila. psittaci
mainly birds
95
spirochetes
long, slender, helical, flexible
free living and non-pathogenic
modified outer membrane
96
B. burgdoferi
```
lyme disease
tick borne
bull's eye rash
spreads through ECM
culture in medium containing rabbit serum
```
97
T. pallidum
syphilis
primary stage- localised infection, days to weeks
secondary stage- systemic, 1 to 3 months
tertiary stage- gummas in bone and soft tissue, neurosyphilis, several years
98
Gram-negative pathogens in the respiratory tract
```
o Bordetella pertussis
o Haemophilus influenzae
o Pseudomonas aeruginosa
o Legionella pneumophila
o Chlamydia pneumoniae
```
99
Gram-negative pathogens in the GI tract
```
o Vibrio cholerae
o Shigella dysenteriae/S. flexneri
o S. enterica sv enteritidis/typhimurium
o Some Escherichia coli serotypes
o Campylobacter jejuni/C. coli
o Helicobacter pylori
o Bacteroides fragilis
```
100
Gram-negative pathogens and meningitis
o Neisseria meningitidis
o Some E. coli serotypes
o Haemophilus influenzae
101
Gram-negative pathogens in the urinary tract
o Some E. coli serotypes
o Proteus mirabilis
o Klebsiella pneumoniae
102
Gram-negative pathogens- STIs
o Neisseria gonorrhoeae
o Chlamydia trachomatis
o Treponema pallidum
103
Gram-negative pathogens in wound infections
o Some E. coli serotypes
o Bacteroides fragilis
o Pseudomonas aeruginosa
104
3 groups of worms
nematodes
trematodes
cestodes
105
nematodes
round worms
intestinal, larva migrans, tissue
106
trematodes
flatworms, flukes
blood, liver, lung, intestinal
107
cestodes
tapeworms
non-invasive, invasive
108
features of helminths
cannot usually reproduce without a period of development outside the body
although they usually produce a large number of larvae or eggs, they cannot increase the burden without re-exposure
109
pre-patent period
interval between infection and appearance of eggs in the stool
110
intestinal nematodes
transmitted from human to human via egg or larvae
| the egg or larva is not usually infectious when first passed and has to undergo a period of development in the soil
111
Ascaris lumbricoides: the large roundworm
cream coloured
15-30cm long
lives a year or more
pre-patent period is 60-75 days
112
loeffler's syndrome
associated with larval migration through lungs
10-14 days after infection
cough, fever, wheeze, eosinophilia
113
Ascaris lumbricoides effects of adult
often asymptomatic
| can be mechanical e.g. intestinal obstruction or malnutrition
114
Ascaris lumbricoides odd presentation
emerging from nose
| perforated eardrum
115
The Hookworm
white worm
1cm in length
life expectancy 1-5 years
116
The Hookworm 2 species
ancylostoma duodenale
| necator americanus
117
The Hookworm clinical features
ground itch- papules at site of entry of the larvae
pulmonary symptoms- mild due to pulmonary migration
most common cause of iron deficiency
118
The Hookworm diagnosis
stool microscopy for eggs
119
The Hookworm treatment
iron supplements
pyrantel
mebendazole
120
Enterobius vermicularis: the pinworm or threadworm
most common helminth infection in the uk
121
Enterobius vermicularis life cycle
adult is resident in large bowel
female adult emerges from anus at night to lay eggs on the perineum
the eggs are infectious after 4 hours are ingested by next host
122
Enterobius vermicularis clinical features
pruritus ani
appendicitis
vaginal penetration- endometritis, infertility
affects whole families
123
Enterobius vermicularis diagnosis
microscopy of sellotape strip from perianal region
124
Enterobius vermicularis treatment
mebendazole
piperazine
pyrantel
125
Trichuris trichiura: the whipworm
2-5cm long
live 1 year
pre-patent period is 70-90 days
partially buried in the mucosa of large bowel
126
Trichuris trichiura clinical features
resident of large bowel
asymptomatic
co exists with ascaris lumbricoides
127
Trichuris trichiura diagnosis
stool microscopy for eggs
128
Trichuris trichiura treatment
mebendazole
| albendazole
129
Strongyloides stercoralis
causes strongloidiasis
2mm long
lies buried in small intestinal mucosa
pre-patent period is 17-28 days
130
Strongyloides stercoralis clinical features
pruritus at site of entry
malabsorption
eosinophilia
hyperinfection syndrome
131
visceral larva migrans
caused by toxocara canis and t.cati (dog and cat roundworm)
mainly a disease of children
diagnose with eosinophilia and serology
treat with mebendazole
132
ocular toxocariasis
```
larvae trapped in retina
see a granulomatous reaction
blindness
diagnose with serology and biopsy
treat with mebendazole
```
133
cutaneous larva migrans
creeping itchy skin eruption
dog hookworms
lesions at site where larvae penetrate
treat with topical or systemic thiabendazole
134
Dracunculus medinensis: The Guinea worm
100cm long
lives one year subcutaneously
incubation period is one year
worm emerges from skin
135
Dracunculus medinensis clinical
localised pain
blister bursting
tetanus or sepsis
136
Dracunculus medinensis diagnosis
drop water on ulcer promotes egg release
137
Dracunculus medinensis treatment
local- wind out worm
| mebendazole
138
Dracunculus medinensis prevention
sieving of water
139
Wuchereria bancroftii
causes elephantiasis
| adults live in lymphatic system and survive 30 years
140
Wuchereria bancroftii diagnosis
demonstration of microfilaria in blood taken at right time of day (2300-0100)
141
Wuchereria bancroftii treatment
diethylcarbamazine
142
Trichinella spiralis
cause of trichinosis
143
Trichinella spiralis clinical picture
```
asymptomatic
GI disturbance associated with worm development
fever, headache, cough
periorbital oedema
myocarditis
pneumonitis
```
144
Taenia saginatum
beef tapeworm
5-10metres long
pre-patent period is 12 weeks
145
Taenia saginatum clinical
asymptomatic
| proglottids may emerge from anus
146
Taenia saginatum diagnosis
stools with eggs and proglottids
147
Taenia saginatum treatment
niclosamide
| praziquantel
148
flukes
blood
liver
lung
bowel
all have snail as an intermediate host
149
schistosomiasis
adult fluke is 12cm long
life span is 3-5 years
schistosoma haematobium- africa, Arabia, Mauritius
schistosoma mansoni- africa
schistosoma japonicum- china, japan, phillippines
150
katayama fever
```
initial immune complex mediated illness
2-4 weeks after exposure
eosinophilia
diarrhoea
cough
hepatomegaly and splenomegaly
```
151
liver flukes
adults resident in human biliary tree
invade liver via biliary tree
opisthorcis filenius
the bovine liver fluke
152
lung flukes
resident in lung
paragonimus westermant
chinese lung fluke
153
intestinal flukes
desident in gut
fasciolopiasis
giant chinese gut fluke
154
intestinal flukes
desident in gut
fasciolopiasis
giant chinese gut fluke
155
m. tuberculosis
tubercolosis
156
m. kansasii
chronic lung infection
157
m. maranium
fish tank granuloma
158
m. ulcerans
buruli ulcer
159
m.leprae
leprosy
160
buruli ulcer formation
```
nodule
small ulcer
large ulcer
deforming
bone destruction
(m. ulceran bacterium)
```
161
buruli ulcer treatment
antibiotics for 8 weeks
wound management
surgery
162
microbiology of mycobacteria
aerobic, non-spore forming, non-motile bacillus
cell wall= high molecular weight lipids
slow growing e.g. tb generation time is 15-20 hours
163
mycobacteria cell wall
weakly gram positive
survives inside macrophages
contains mycolic acids and lipoarabinomannan
164
mycobacterial slow growth
slow reproduction so slow growth in humans (slow onset of disease) and on agar
it responds slowly to treatment as well
165
mycobacteria acid fast bacilli
need this stain as the high lipid content in the walls make it gram resistant
ziehl-neelsen- carbol fuchsin, acid alcohol, methylene blue
166
mycobacterial slow growth in culture
first need decontamination steps to kill off other rapid growing bacteria
solid culture= egg based lowenstein jensen, microspoy positive material 2-4 weeks, negative 4-8 weeks
liquid culture= 1-3 weeks, automated systems BACTEC mycobacterial growth indicator tube
167
TB reactivation risk after exposure
risk = 10% lifetime risk, most in first 2 years then 0.1% a year
increased risk= young infants and elderly, malnutrition, intensity of exposure and immunosuppression
168
tuberculoid leprosy
associated with tissue hypersensitivity and granulomata
paucibacillary lesions with low numbers of mycobacteria
tissue damage e.g. nerves
predominate th1 biased cd4+ t cell responses- IFN-g and TNF-a production
169
leptromatous leprosy
lesions full of bacilli but little or poorly formed granulomata
extensive skin lesions
predominant th2 biased cd4+ t cell response- IL4,5,10 production
170
primary TB
bacilli taken into lymphatics to hilar lymph nodes
171
latent TB
cell mediated immune response from t-cells
primary infection is contained but immune response persists
no clinical disease but detectable immune response to TB on skin test
172
pulmonary tuberculosis
granuloma forms around -bacilli settle in the apex
- the apex has more air and less blood supply so fewer cells for immune response
- immune response and necrosis results in abscess of bacilli forming and caseous material coughed up leaving cavity
- can occur immediately or after latent TB
173
TB spreads beyond lungs
enters lymph nodes
```
genitourinary tb
tb meningitis
miliary tb
pleural tb
bone and joint tb
```
174
TB spreads beyond lungs
enters lymph nodes
```
genitourinary tb
tb meningitis
miliary tb
pleural tb
bone and joint tb
```
175
common viral infections
```
respiratory viruses
rash causing viruses
herpes group
hepatitis group
enteroviruses
diarrhoea causing viruses
HIV
```
176
diseases and viruses
same virus can cause different diseases e.g. enteroviruses cause resp infections and meningitis
different viruses can cause the same disease e.g. different hepatitis viruses
177
basic properties of viruses
only grow inside cells
possess only one type of nucleic acid
have an outer protein coat, some have a lipid envelope as well
essentially inert outside the host cell
178
are viruses living
have nucleic acid
have outer protein coat
can replicate once inside a living host cell and pass on its genetic code- using host enzymes
179
are viruses non- living
non cellular
no cell wall
cannot replicate by themselves
have no organelles
180
attachment (viral replication)
viral and cell receptors
viruses need specific receptors to attach to cells to enter them
this dictates the type of cells viruses can infect
181
cell entry (viral replication)
only central viral core carrying nucleic acid and some proteins enter the cell
182
interaction (viral replication)
using cell materials such as enzymes, amino acids and nucleotides
they replicate
subvert host cell defence mechanisms
183
replication (viral replication)
may localise in nucleus, cytoplasm or both
| produce progeny viral nucleic acid and proteins
184
assembly (viral replication)
occurs in nucleus e.g. herpes virus or cytoplasm e.g. polio or at cell membrane e.g. influenza
185
release (viral replication)
via lysis of a cell or by exocytosis
186
viruses causing disease
- damage by destruction of host cells
- by modification of cell structure or function
- involving over-reactivity of the host as a response to infection
- damage through cell proliferation
187
pathogenesis of rotavirus
- following ingestion, rotaviruses infect epithelia cells of the small intestine
- there is shortening and atrophy of the villi and flattening of epithelia cells
- decreases surface area of small intestine and limits production of digestive enzymes
- they suffer malabsorption
- causes diarrhoea
188
infection with hepatitis B
majority are asymptomatic
there is a massive antibody and CTL response- destroying virally infected hepatocytes
can cause extensive liver damage
189
hepatitis B virus and chronic carrier state
- steady state between virus replication in host cells and host defence response
- limited by sustained viral replication
- hepatocyte regeneration
- no clinical symptoms
190
development of cervical carcinoma
- HPV types 16 and 18 infect suprabasal layer of genital system
- partial replication and gradual movement of cells to mucosal surface through natural wear and tear
- HPV genome is integrated into host cell chromosome
- viral gene expression by HPV E2 protein is lost and HPV E6 and E7 are expressed
- two cell growth and proliferation suppressor proteins are prevented from operating
- excessive cell growth and proliferation occurs and cervical cell carcinoma results
191
viral evasion at cellular level
latency: allows viruses to cause life threatening disease in the immunosuppressed
spreads cell to cell
192
viral evasion and molecular level
antigenic variability
prevention of host cell apoptosis
down regulation of interferon and other host cell defence proteins
interference with host cell antigen processing pathways
193
viral diagnosis
electron microscope
cell culture
antigen- viral protein detection
serology
194
viral treatment
treat with antivirals
prevent with vaccines
195
viral treatment
treat with antivirals
prevent with vaccines
196
fungi biology
```
eukaryotic
chitinous cel wall
exist as yeast or mould
heterotrophic
move by means of growth or spores
```
197
yeast vs mould
yeast= single celled organisms that divide by budding. small. <1% of fungal species
moulds= multicellular hyphae. form spores.
dimorphic fungi= switch between the two depending on the conditions
198
common fungal infections
nappy rash
athletes foot
fungal nail infection
fungal asthma
199
immunocompromised hosts and fungal disease
candida line infections
invasive aspergillosis
pneumocystis
mucormycosis
200
post surgical patients and fungal disease
intra abdominal infection
201
healthy host and fungal disease
fungal asthma
| travel associated fungal infection
202
diagnosing fungi
microscopy and histology
culture
serology
203
mucosal candidiasis
```
thrush
treat with topical antifungals and oral fluconazole
associated with:
- diabetes
- immunocompromised
- antibiotics
- pregnancy
```
204
invasive aspergillosis and galactaomannan
chest focus more common
culture is insensitive
can cause brain disease
more common in immunocompromised
205
pneumocystis pneumonia
immunocompromised patients
unable to culture
treat with co-trimoxazole
206
treating fungal disease- selective toxicity
aims of drug is to achieve inhibitory levels of agent at the site without host cell toxicity
relies upon identifying molecules with selective toxicity:
- ones that dont exist in humans
- different to human analogue
- human cells recover from toxicity by alternative metabolic pathways
207
fungal cell targets- DNA/RNA and protein synthesis
similar to mammalian
drug e.g. fluctosine
208
fungal cell targets- cell wall
mannoproteins
B1,3 and 1,6 glucan
chitin
dont exist in humans
drug e.g. echinocandins
209
fungal cell targets- plasma membrane
ergosterol
human membrane contains cholesterol instead
drug e.g. amphotericin, azoles, terbinafine
210
ergosteol synthetic pathway
agents act early in pathway will be cidal
| those acting at later stages will be fungistatic
211
allylamines
reversible inhibition of squalene epoxidase
fungicidal
absorbed well but extensive first metabolism so bioavailability is 45%
used to treat dermatophytes
212
azoles
dose dependent inhibitors of 14alpha-sterol demethylase
fungistatic
newer azoles have increase spectrum of activity
213
spectrum of activity of azoles
determined by degree of inhibition of 14alpha-sterol demethylase and secondary targets
214
azole adverse effects
relatively safe
drug interaction due to CYP450 metabolism
alopecia with long term fluconazole
30% on voriconazole suffer reversible visual disturbances
215
azole resistance
multiple mechanisms in candida:
target site modification
-increased expression of ERG11
-efflux
216
polyenes
- amphoteric molecules
- disruption caused by insertion of molecule into the membrane displaces and affects activity of membrane bound proteins
- forms pores so fungicidal
- 10x lower affinity for cholesterol but still can cause toxicity
217
echinocandins
```
inhibit 1,3 beta glucan synthase
fingicidal to susceptible yeasts
fungstatic to moulds with activity at hyphal tip
IV only
few side effects
```
218
echinocandins
```
inhibit 1,3 beta glucan synthase
fingicidal to susceptible yeasts
fungstatic to moulds with activity at hyphal tip
IV only
few side effects
```
219
protozoa
single cell with nucleus
| >30,000 species
220
5 groups of protozoa
```
flagellates
amoebae
sporozoan
ciliates
microsporidia
```
221
flagellates
leishmaniasis
trichomonas vaginalis
giardiasis
222
amoebae
amoebiasis
223
sporozoan
cryptosporidiosis
toxoplasma gondii
malaria (plasmodium)
224
leishmaniasis
spread by bite of the sandfly
| >20 species that affect humans
225
leishmaniasis clinical pictures
```
cutaneous= ulceration
mucocutaneous= ulceration
```
both can cause social rejection and scarring
visceral= fever, weight loss, hepatomegaly, anaemia
226
thrichomonas vaginalis
```
sexually transmitted
asymptomatic
dysuria
yellow frothy discharge
treat with metronidazole
```
227
giardiasis
```
giardia lamblia
faecal-oral spread
diarrhoea
cramps
treat with metronidazole
```
228
amoebiasis
```
enteraemoeba histolytica
faeco-oral spread
dysentery
liver and lung abscesses
treat with metronidazole
```
229
cyrptosporidiosis
```
waterborne
diarrhoea
womiting
oocytes seen in stool
sever in immunocompromised
```
230
toxoplasmosis
ingestion of contaminated food and water
| acute maternal infection can be fatal in pregnancy
231
toxoplasmosis can cause
disseminated disease
toxoplasma encephalitis
chorioretinitis
232
5 species of malaria
```
Plasmodium falciparum
Plasmodium ovale
Plasmodium vivax
Plasmodium malariae
Plasmodium knowlesi
```
233
test for malaria
blood film
234
symptoms of malaria
```
fever
chills
headache
myalgia
fatigue
diarrhoea
```
235
signs of malaria
anaemia
jaundice
hepatosplenomegaly (big spleen and liver)
236
life cycle of malaria
- mosquito bites infected human and ingests plasmodium gametocytes
- the gametocytes are within midgut and undergo development- becomes sporozoites in salivary gland
- they're injected into blood and infect human liver hepatocytes
- develop into schizont and bursts out and infects red blood cells
- this stage lasts 48 hours with haemolysis causing anaemia and jaundice
237
p. falciparum
-The pathophysiology of complicated malaria is mostly down to the infected RBCs ability to
adhere to endothelial cells
-RBCs infected with p. falciparum have proteinaceous knobs on the surface that bind to
endothelial cells in the vessels and other RBCs
-This can cause small vessels to become obstructed by clumps of red blood cells causing hypoxia of the tissues, microinfarcts in brain and lung
238
complicated cerebral malaria
```
vascular occlusion
drowsiness
raised intracranial pressure
seizures
coma
```
239
complicated malaria and acute respiratory distress
```
vascular occlusion
anaemia
lactic acidosis
increased vascular permeability
hypoxia
pulmonary oedema
```
240
complicated malaria and renal failure
vascular occlusion
dehydration- hypotension
haemolysis- haemoglobulinuria
proteinuria
fatigue
haematuria
241
complicated malaria and bleeding
thrombocytopenia
activation of coagulation cascade
worsened anaemia
242
complicated malaria and shock
anaemia
bleeding
gram -ve sepsis
increased vascular permeability
hypotension
tachycardia
pale
243
malaria treatment
complicated= IV artesunate, IV quinine+doxycycline
244
supportive measures for malaria
```
cerebral= anti-epileptics
ARD= oxygen, diuretics, ventilation
renal failure= dialysis
sepsis= antibiotics
bleeding= blood products
```
245
malaria relapses
p.ovale and vivax can form hypnozoites in the liver- lying dormant
primiquine eliminates this
246
antibiotics
agents produced by microorganisms that kill or inhibit the growth of other microorganisms
247
antimicrobials
most agents currently used are semi-synthetic derivatives so = antimicrobials
antifungal, antibacterial, antihelminitic, antiprotozoal and antiviral
248
antibiotics as antibacterials
antibiotic tends to= antibacterial
bind to target site on bacteria
give time and support for the immune system to deal with an infection
249
antibiotics affecting bacterial cell wall synthesis
beta lactams= penicillins, cephalosporins, carbapenems, monobactams
glycopeptides= vancomycin and teicoplanin
250
beta lactam antibiotics
disrupt peptidoglycan production by binding covalently and irreversibly to PBPs
to do so it diffuses through the cell wall
cell wall is disrupted and lysis occurs
gram positive is more susceptible
251
antibiotics affecting bacterial nucleic acid synthesis
DNA gryase- quinolines
| RNA polymeras- rifampin
252
antibiotics affecting bacterial protein synthesis
ribosome 30s subunit- tetracyclines, aminoglycosides
ribosome 50s subunit- macrolides, chloramphenicol
253
antibiotics affecting bacterial folate synthesis
sulphonamides
| trimethoprim
254
bacteria and accidental damage
```
destroy phagocytes or cells in which bacteria replicate
endotoxins
exotoxins
inflammation
diarrhoea
```
255
bacteriostatic
```
prevents growth
by preventing multiplication
kill >90% in 18-24 hours
inhibit protein synthesis, DNA replication or metabolism
MBC to MIC ratio >4
```
256
bactericidal
kill bacteria
>99.9% killed in 18-24 hours
inhibit cell wall synthesis
257
minimum inhibitory concentration
concentration required to stop bacteria from multiplying
258
lowest MIC does not equal best antibiotic
drugs must attach to binding site and occupy an adequate number of binding sites
to work effectively they should remain on binding site for a sufficient period in order for metabolic processes to be inhibited
259
concentration dependent killing
key parameter is how high the concentration is above MIC
260
time dependent killing
key parameter is the time the serum concentrations remain above the MIC during dosing interval
261
antibiotic considerations
release and absorption
distribution to site
half life and elimination
262
other antibiotic considerations
```
are they safe
side effects
renal function
liver function
pregnancy
drug interactions
```
263
changing antibiotic target site
bacteria changes molecular configuration of binding site or masks it
264
destroying the antibiotic
e.g. beta lactam ring of penicillin is hydrolysed by bacterial enzyme beta lactamase
265
preventing antibiotic access
modify bacterial membrane porin channel size, numbers and selectivity
266
removing bacteria from bacteria
proteins in bacterial membranes act as an export or efflux pumps- so antibiotic levels are reduced
267
intrinsic resistance
subpopulations of a species will be equally resistant
268
acquired resistance
bacterium that was previously susceptible obtains ability to resist the activity of an antibiotic
269
MRSA
staphylococcal cassette chromosome mec, contains resistance gene
270
VRE
plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding
271
ESBL
mutation at the active site extended range of antimicrobial resistance to form extended spectrum beta lactamase (ESBL) inhibition
plasmid spread resistance
272
AmpC b-lactamase resistance
broad spectrum penicillin, cephalosporin resistance
| encoded on the chromosome in bacteria
273
beta lactams
group of drugs that contain beta lactam ring- detroy cell walls
penicillin V, amoxicillin, cephalexin
274
cephalosporins
beta lactams
good for penicillin allergy
better for resistance bacteria
275
gram positive antibiotics
thick cell wall so need simple cell wall weapon
276
gram negative antibiotics
thin cell wall so need a different weapon
277
methicillin resistant staphylococcus aureus
describes all staph that are resistant to beta lactams
278
macrolides
clarithromycin and erythromycin
for gram positives and atypical pneumonia pathogens
use in penicillin allergy and severe pneumonia
279
linosamides
clindamycin
gram positives e.g. s. aureus
use for cellulitis or necrotising fasciitis
280
tetracyclines
doxycycline
broad spectrum but mainly gram positive
use for cellulitis if penicillin allergy and chest infections
281
quinolones
ciprofloxacin
for gram negatives
urinary tract infections, gall bladder infections, abdominal infections
282
beta lactams for gram negative
amoxicillin- clavulante, cefuroxime, meropenem, ceftriaxone
283
beta lactams for gram negative
amoxicillin- clavulante, cefuroxime, meropenem, ceftriaxone
284
HIV genome
```
codes for 9 genes
Gag
Pol
Env
Tat
Nef
Vif
Vpr
Vpu
Rev
```
285
prevention strategies for HIV
```
HIV testing
early diagnosis
sti testing
HAART
screening of blood products
microbicides
male circumcision
post-exposure prophylaxis
Pre-exposure prophylaxis
behavioural prevention strategies for HIV
future
```
286
features that make HIV successful
transmitted by sexual intercourse
latency so individuals don't know they're spreading the disease
stops immune system functioning
ineffective at replication so mutates every time
287
HIV origins
HIV-1 = transmission of simian immunodeficiency virus (SIV cpz) from chimps to humans
HIV-2 = arose from SIV sm
288
HIV types
Main, outlying and new groups
| main separated into A-D, F-H, J-K
289
HIV replication
- attachment via gp120 to CD4 receptors
- entry
- uncoating
- reverse transcription -error prone
- genome integration by integrase enzyme
- transcription of viral RNA
- splicing of mRNA and translation into proteins
- assembly
- budding
290
HIV receptors
their glycoprotein- gp120 binds to human CD4 receptors
291
HIV genes: Pol
encodes reverse transcriptase, integrase, protease
292
HIV genes: Env
encodes envelope proteins
293
HIV genes: Nef
increases infectivity
294
HIV genes: Tat
contributes to viral replication
295
HIV genes: Gag
encodes structural proteins
296
HIV genes: Rev
binds to viral RNA and allows export from nucleus and regulates RNA splicing
297
cell tropism- infected cells in HIV
```
CD4 cells
macrophages
dendritic cells
CD34 bone marrow progenitors
astrocytes
```
298
initial HIV infection
- virus enters via mucosa (vaginal, rectal etc.)
- local infection within mucosal macrophage then spreads to other cells
- as these are APCs they will migrate to local lymph nodes and T cells
- infection spills into blood stream
299
mechanism for CD4+ T cell depletion
direct cytotoxicity of infected cells
activation induced death
decreased production due to infected progenitors in bone marrow
300
immune system consequences of HIV
decreased number and function of CD4 t lymphocytes
excessive activation of immune system
decreased proliferation in response to antigens
decreased macrophage function
301
sanctuary sites for HIV
genital tract
CNS
GI tract
bone marrow
302
reservoir cells for HIV
macrophages
T cells
microglia
303
UNAIDS 90/90/90 goals
90% of people with HIV diagnosed
90% of diagnosed on ART
90% viral suppression for those on ART by 2020
304
HIV transmission routes
blood
sexual
vertical- mother to child
305
post-exposure prophylaxis
PEP
treatment commences within 72 hours of exposure
continued for one month
306
Pre-exposure prophylaxis
PrEP
good evidence for effectiveness
ongoing trial in the UK to address questions such as duration of dose
307
behavioural prevention strategies for HIV
sex education
avoid concomitant sexual partners
reduce high risk sexual partners
consistent condom use
308
future prevention strategies for HIV
vaccines
309
benefits of knowing HIV status
access to appropriate treatment
reduction on mortality
reduction in vertical transmission
reduction of sexual transmission
310
high risk behaviours of HIV
sex with people from high prevalence groups e.g. subsaharan africa and thailand etc.
multiple sexual partners
rape in high prevalence localities
311
consider HIV if recurring conditions, e.g.
```
shingles
oral candidiasis
flu like symptoms
rash
unexplained weight loss/ diarrhoea
unexplained lymphadenopathy
```
312
screening tests for HIV
p24 antigen test
| test at 4 weeks, if negative repeat at 8 weeks if high suspicion
313
managing the result of HIV
negative- repeat if within window
| positive-arrange appointment within 48 hours, explain test is reactive and needs further investigation
314
partner notification and HIV
discuss with all HIV infected people
length of look back depends on circumstances
encourage them to inform their partners or agree to notification
document discussion
discuss consequences of reckless transmission
315
criminalisation of HIV
only those who know their status are criminally liable
316
confidentiality definition
Right of an individual to have personal, identifiable medical information kept private. Such information should be available only to the physician of record and other health care and
insurance personnel as necessary
317
confidentiality and HIV
allows disclosure to known sexual partner if at risk and unaware
must inform patient you are doing so unless it endangers the contact
don't reveal identity of patient
318
markers of HIV
CD4 count
| HIV viral load
319
seroconversion
period of time during which HIV antibodies develop and become detectable
320
acute HIV syndrome
usually takes 2-4 weeks
similar to glandular fever or flu
can present with opportunistic infections
non-specific symptoms
321
HIV clinical latency
undiagnosed- the immune system takes control and CD4 increases
overtime CD4 does begin to decline
can then present with more opportunistic infections
322
development of HIV symptoms
shingles
candida
oral hairy leukoplakia
recurring infections
323
acquired immune deficiency syndrome
AIDs
| CD4<200 and/or AIDs defining illness present
324
AIDS defining illnesses
pneumocystis pneumonia
other respiratory infections
TB
325
pneumocystis pneumonia
most common AIDS defining illness
| most common opportunistic infection
326
symptoms of pneumocystis pneumonia
fevers
dry cough
chest pain
drop in O2 sats
327
tests for pneumocystis pneumonia
chest xray- can be normal
ABG test for hypoxia
induced sputum
328
treatment of pneumocystis pneumonia
antibiotics- co-trimoxazole
| and steroids
329
HIV clinical latency
undiagnosed- the immune system takes control and CD4 increases
overtime CD4 does begin to decline
can then present with more opportunistic infections
330
development of HIV symptoms
shingles
candida
oral hairy leukoplakia
recurring infections
331
acquired immune deficiency syndrome
AIDs
| CD4<200 and/or AIDs defining illness present
332
AIDS defining illnesses
pneumocystis pneumonia
other respiratory infections
TB
333
pneumocystis pneumonia
most common AIDS defining illness
| most common opportunistic infection
334
symptoms of pneumocystis pneumonia
fevers
dry cough
chest pain
drop in O2 sats
335
tests for pneumocystis pneumonia
chest xray- can be normal
ABG test for hypoxia
induced sputum
336
treatment of pneumocystis pneumonia
antibiotics- co-trimoxazole
| and steroids
337
TB and HIV
can present at any CD4 count
atypical presentations with lower CD4 count
all patients with TB should be tested for HIV
338
CNS presentations of HIV
toxoplasmosis- reactivation of latent infection
| meningitis- higher incidence and mortality in HIV
339
cancers and HIV
increase in any cancer associated with a virus
HepB/B- hepatocellular carcinoma
human papilloma virus- cervical cancer
herpes 8- kaposi's sarcoma
340
kaposi's sarcoma
single to multiple lesions
| on the skin, mouth, respiratory tract, GI tract
341
late diagnosis of HIV
increased transmission
increased morbidity
increased mortality
342
highly active antiretroviral therapy
HAART
3+ antiretroviral drugs
act on different points in HIV replication cycle
aim to reduce viral loads to undetectable levels- not a cure
343
how do antiretroviral drugs function
fusion/entry inhibitors
reverse transcriptase inhibitors
integrase inhibitors
protease inhibitors
344
HIV resistance
1 mutation in every 2 new viruses produced
develop drug resistance through:
non-adherence (missing one or two doses)
drug-drug interactions
345
avoiding HIV resistance
good drug adherence
| checking drug interactions
346
groups at risk of HIV
```
men who have sex with men
heterosexual women
injecting drug users
commercial sex workers
heterosexual men
truck drivers
migrant workers
```
347
problems for antiretroviral treatment in developing countries
```
awareness
procurement/delivery
clinical services
cost
adherence
efficacy
co-morbidities
```
