Microbiology Flashcards
(666 cards)
1
Q
what are examples of bacteria and viruses, from largest (30μm) to smallest (less than 1μm)
A
trypanosoma gambiense entamoeba histolytica borrellia recurrentis treponema pallidum bacillus anthracis escherichia coli staphylococcus aureus rotavirus chlamydia trachomatis vaccinia virus influenza virus wart virus poliovirus
2
Q
what is bacterial nomenclature? what is an example?
A
staphylococcus (genus) aureus (species)
3
Q
what is a pathogen?
A
organism that causes or is capable of causing disease
4
Q
what is a commensal?
A
organism which colonises the host but causes no disease in normal circumstances
5
Q
what is an opportunist pathogen?
A
microbe that only causes disease if host defences are compromised
6
Q
what is virulence/pathogenicity?
A
the degree to which a given organism is pathogenic
7
Q
what is asymptomatic carriage?
A
when a pathogen is carried harmlessly at a tissue site where it causes no disease
8
Q
what is the diameter of the smallest body that can be resolved and seen clearly with the naked eye?
A
100μm
9
Q
what are colonies?
A
bacteria and fungi form macroscopically visible structures comprising at least 10^8 cells (when propagated on solid media)
10
Q
what are the three domains of life?
A
bacteria, archaea and eukarya
11
Q
what is the anatomy of a bacterial cell?
A
- cytoplasm bound peripherally by a very thin, elastic and semi-permeable cytoplasmic/plasma membrane (phospholipid bilayer)
- the cell wall is outside and closely covering the membrane, which is porous and permeable
- cell division mediated by actin-like protein, FtsZ
- septum/cross wall
- S-layer is a variably demonstrated ordered protein layer
- capsule
- fimbriae
- flagellum
- sex pili
12
Q
what combines to produce the cell morphology and characteristic patterns of arrangement?
A
the exact pattern of cell division and the structures associated with the cell wall and cytoplasmic membrane (collectively the cell envelope)
13
Q
what are the two basic shapes of bacterial cells?
A
coccus: spherical
bacillus: rod shaped
14
Q
what shape are bacterial cocci?
A
spherical
15
Q
what shape are bacterial bacilli?
A
rod shaped
16
Q
what are variations of bacilli?
A
vibrio: comma shaped
spirillum and spirochaete: spiral
filamentous
17
Q
what are the shapes and characteristic groupings of various bacterial cells?
A
- diplococci
- streptococci
- staphylococci
- sarcina
- bacillus
- vibrio
- spirillum
- actinomyces
18
Q
what are the structures in bacteria cytoplasm that correspond to eukaryotic actin, tubulin and intermediate filaments?
A
MreB, FtsZ and crescentin respectively
19
Q
what types of larger structures occur in some species of bacteria under specific growth conditions?
A
spores or inclusion bodies of storage products e.g. volutin (polyphosphate), lipid (poly-beta-hydroxyalkanoate or triacylglycerol), glucogen or starch
20
Q
what is a capsule?
A
protective gelatinous covering layer outside the bacterial cell wall
21
Q
what is a microcapsule?
A
a bacterial capsule that is too thin to be resolved with the light microscope
22
Q
what is loose slime?
A
soluble large-molecular material that may be dispersed by the bacterium into the environment
23
Q
what are flagella?
A
- protein-based filamentous appendages that protrude outwards from the cell wall of bacteria
- organs of locomotion
24
Q
what are fimbriae/pili?
A
- hair like structures on bacteria
- mediate adhesion via specific receptor-ligand interactions at their tip
25
how do bacteria store/package DNA?
- genetic info is mostly contained in a single, long molecule of double-stranded DNA
- DNA can be extracted in the form of a closed circular thread about 1 mm long
- condenses and loops macromolecule into a supercoiled state
26
what are plasmids?
additional fragments of episomal (extrachromosomal) DNA contained in the bacterium
27
how many alleles of each gene do bacteria have?
- bacteria are essentially haploid organisms with only one allele of each gene per cell
- may be multiple copies of chromosomes and plasmids
28
what is the function of nucleoid-associated proteins (NAPs) in bacteria?
- function in the cytoplasm rather than within a membrane-bound nucleus
- NAPS e.g. H-NS and IHF exert effects on prokaryotic gene expression
- synthesis of mRNA and protein are directly coupled in bacteria
29
what is the size and composition of bacterial ribosomes?
- 10-20 nm
| - sedimentation coefficient of 70S: composed of a 30S and 50S subunit
30
what is the composition of eukaryotic ribosomes?
40S and 60S subunits in the 80S
31
what do multiple ribosomes form?
multiple ribosomes attach to single mRNA molecules to form polysomes
32
what are polysomes?
multiple ribosomes attached to single mRNA molecules
33
what is the thickness/structure of bacterial cytoplasmic membrane?
- 5-10 nm thick
- consists mainly of phospholipids and proteins
- contains integral, transmembrane, peripheral and anchored proteins
- protein rich, little space for phospholipids
34
what is the function of bacterial cytoplasmic membrane?
multifunctional nature
- protein secretion, packaging and processing
- electron transport and oxidative phosphorylation
35
what is the structure/characteristics of the cell wall?
- lies immediately external to the cytoplasmic membrane
- 10-25 nm thick
- strong, rigid (some elasticity), openly porous (permeable to solute molecules smaller than 10kDa in mass and 1 nm in diameter)
36
what is the function of the bacterial cell wall?
- supports the weak cytoplasmic membrane against the high internal osmotic pressure
- maintains the characteristic shape of the bacterium in its form
37
what are the internal osmotic pressures in Gram-positive and Gram-negative bacteria?
25 and 5 atm respectively
38
what is the main strengthening component of the bacterial cell wall?
peptidoglycan (syn. mucopeptide or murein)
39
what is peptidoglycan composed of?
N-acetylglucosamine and N-acetylmuramic acid molecules linked alternatively in a chain
40
what is the murein sacculus?
heteropolymer (peptidoglycan) forms a single molecular continuous sac external to the cytoplasmic membrane
41
what is involved in the Gram-stain procedure?
- distinguishes bacteria as Gram-positive or Gram-negative
- according to whether or not they resist decolouration with acetone, alcohol or aniline oil after staining with a triphenyl methane dye, e.g. crystal violet, and subsequent treatment with iodine
42
what are the results of the Gram stain procedure?
- Gram-positive bacteria resist decolouration and remain stained a dark purple colour
- Gram-negative bacteria are decolorized, and then counterstained light pink by the subsequent application of safaranin, neutral red or dilute carbol fuchsin
43
what peptides do the N-acetylmuramic acid units of peptidoglycan carry?
- L-alanine
- D-glutamic acid
- either meso-diaminopimelic acid (Gram-negative bacteria) or L-lysine (Gram-positive bacteria)
- D-alanyl-D-alanine
44
what is the strength of peptidoglycan walls given by?
cross-links that form between adjacent strands
- may be formed directly between meso-diaminopimelic acid or L-lysine of one strand and the penultimate D-alanine of the next, or through an interpeptide bridge composed of up to 5 amino acids
45
what can interfere with construction of cell wall peptidoglycan?
several antibiotics
46
what is lose in the cross-linking reaction in cell wall peptidoglycan?
terminal D-alanine
47
what do many Gram-positive bacteria contain in their cell wall?
- large amounts of teichoic acid (a polymer of ribitol or glycerol phosphate complexed with sugar residues) interspersed with the peptidoglycan
- some of this material (lipoteichoic acid) is linked to lipids buried in the cell membrane
48
what are the components of the envelope of the Gram-positive bacteria cell wall? what do they contain?
capsule: capsular polysaccharide
cell wall: peptidoglycan with teichoic acid polymers
cytoplasmic membrane: phospholipid bilayer with various membrane proteins, enzymes and permeases
49
what is the difference between teichoic acid and lipoteichoic acid in peptidoglycan cell wall in Gram-positive bacteria?
- teichoic acid is just in the peptidoglycan cell wall
| - lipoteichoic acid is linked to lipids buried in the cell membrane
50
what is teichoic acid?
a polymer of ribitol or glycerol phosphate complexed with sugar residues
51
what is a structure of Gram-negative bacteria that Gram-positive bacteria don't have?
- second outer membrane external to the peptidoglycan layer
| - unit membrane in which the outer leaflet is largely composed of lipopolysaccharide (LPS)
52
what does the second outer membrane of Gram-negative bacteria contain?
- composed mainly of LPS
| - contains associated proteins with functions including selective permeability (porins) and attachment (adhesins)
53
what properties does the outer membrane confer on Gram-negative bacteria?
- protects peptidoglycan from effects of lysozyme
| - impedes the ingress of many antibiotics
54
what is N-acetylmuramic acid derived from?
N-acetylglucosamine by the addition of a lactic acid unit
55
how is peptidoglycan formed?
- each N-acetylmuramic acid molecule is substituted with a pentapeptide
- an N-acetylglucosamine molecule is joined to the muramylpentapeptide within the cell membrane
- unit is transferred to growth points in the existing peptidoglycan, where adjacent strands are cross-linked
56
what breaks the bond between N-acetylmuramic acid and N-acetylglucosamine?
lysozyme
57
what is contained within the outer membrane in Gram-negative bacteria?
- LPS
| - porins
58
what is contained within the cell wall of Gram-negative bacteria?
- peptidoglycan
- lipoprotein
- periplasmic enzymes
59
what is contained within the inner membrane of Gram-negative bacteria?
- phospholipid bilayer with various membrane proteins, enzymes and permeases
60
what are the differences between the peptidoglycans of Gram-positive and Gram-negative organisms?
Gram-positive: cross-linking occurs through a peptide bridge (pentaglycine in S. aureus)
Gram-negative: direct cross linking
- terminal D-alanine is lost in both cases
61
what is the peptide structure of Gram organisms/peptidoglycans?
N-acetylmuramic acid linked to L-alanine linked to m-DAP to two D-alanine
62
what is involved in direct cross-linking?
m-DAP crosslinking
63
what do components of LPS form? what the core structure?
- core structure lipid A
| - form endotoxin, which when released into the bloodstream, may give rise to endotoxic shock
64
what is the structure of mycobacteria?
- a third type of cell envelope is characteristic of mycobacteria
- causal agents of TB and leprosy
- peptidoglycan layer is covalently linked on its outer aspect to arabinogalactan, which is itself substituted with unique lipids (mycolic acids)
65
what are mycolic acids? where are they found?
- beta-hydroxy fatty acids consisting of 60 to 90 carbon residues
- together with non-covalently linked free lipids, form an extremely hydrophobic external layer which also contains porins
- found in mycobacteria
66
what property does mycobacteria's envelope structure confer?
acid fast staining by methods such as Ziehl-Neelsen and phenol-auramine procedures
67
what is involved in the Ziehl-Neelsen method? what can it detect?
- detects the tubercle bacillus and other mycobacteria
- mycolic acids provide a barrier to simple aqueous stains
- when permeability is altered by heating or phenol, concentrated solutions of basic fuchsin and fluorescent dyes auramine and rhodamine can produce well-stained cells that resist decolorisation by strong acids in alcohol
68
how are decoloured non-acid-fast organisms counterstained?
in a contrasting colour with methylene blue or malachite green
69
how can modifications of the ZN method be useful?
for the demonstration of bacterial endospores and organisms such as Nocardia spp. and cysts of some protozoa, notably Cryptosporidium spp.
70
when are the continuous and relatively amorphus layers external to Gram envelopes called capsules, and when are they called microcapsules?
capsules: when the layer is fully hydrated and resolvable by light microscopy
microcapsule: when it is narrower, and detectable only by indirect, serological means or by electron microscopy
71
what does does the capsular gel consist of?
largely of water and has only a small content of solids
| - in most species, the solid material is a complex polysaccharide, and in others its main constituent is polypeptide
72
what is loose slime?
an amorphous, viscid, colloidal material secreted extracellularly by some bacteria
73
what are the roles of capsules in bacteria?
- protect against phagocytosis, the lytic action of complement and bacteriophage invasion
- antibodies directed against capsular antigens can protect against infection
- protect cells against desiccation
- typing of bacteria
74
what does the production of extracellular polysaccharides provide?
a matrix within which biofilm formation can take place
75
what are the types of arrangements of flagella?
- peritrichous/lateral: originate from the sides of the cell
| - polar: originate from one or both ends
76
what does the external portion of a flagellum consist of?
polymer of a single protein, flagellin
77
what does the basal region of the flagellum consist of?
multiple subunits that anchor and power the organ
78
how is the flagellar motor powered?
directly: by the protein gradient created across the cytoplasmic membrane by electron transport
79
how does Escherichia coli show chemotactic behaviour?
- alteration between the anti-clockwise and clockwise motion of the flagella effects, respectively, linear or tumbling motility
- intervals between these two patterns are modulated by chemical signals in the environment
80
what is the number/appearance of fimbriae?
100-500 per cell
0.1-1.5 μm in length
short
4-8 nm in width
81
how are fimbriae categorised? give examples of different types
- dimensions, antigenic and phenotypic properties
- types 1 and 2, P type
- present in both Gram-positive and Gram-negative bacteria
82
what are the roles of fimbriae?
important in mediating adhesion between the bacterium and host cells (recognised in the phenomenon of haemagglutination, a property of type 1, mannose sensitive pili)
83
what are sex pili? what are their roles?
- longer than fimbriae
- confer ability to attach specifically to other bacteria that lack these appendages
- initiate the process of conjugation
- act as receptor sites for certain bacteriophages described as being donor specific
84
what are the types of bacterial growth?
growing (vegetative), stationary or dead; uniform in their properties
85
at what levels does bacteria adapt to the environment?
phenotypic and genotypic levels
86
what is an endospore?
some bacteria, e.g. those of genera Bacillus and Clostridium, develop a highly resistant resting phase or endospore, whereby the organism can survive in a dormant state through long periods of starvation or adverse environmental conditions
87
what happens in sporulation and germination?
- each vegetative cell forms only one spore
- in subsequent germination each spore gives rise to a single vegetative cell
- doesn't involve multiplication
88
what are sporulation stimuli?
classically starvation or transition from growth to stationary phase
89
what is the end result of sporulation?
a morphologically distinct structure, the endospore, within the mother cell
90
what are the appearances of spores?
- in unstained preparations, it has greater refractility
- larger than lipid inclusion granules and is often ovoid
- in phase-contrast microscopy, mature ungerminated spores are phase bright and immature germinated spores are phase dark
- when mature, spores resist colouration by simple stains
91
what are the types of spore appearances?
varies according to the species
- spherical, ovoid or elongated
- occupying a terminal, subterminal or central position
- being narrower than the cell, broader or bulging it
92
what is an exosporium?
additional, apparently loose covering of spores
93
why are spores more resistant than vegetative cells?
- high content of calcium and dipicolinic acid
- low content of water
- very low metabolic and enzymic activity
94
what is reactivation of a spore called?
germination
95
when does germination of a spore occur? what does it involve?
- occurs in response to specific stimuli that are related to external conditions favourable to growth
- irreversible and involved rapid degradative changes
- spore loses its heat resistance and its dipicolinic acid; loses calcium; becomes permeable to dyes and its refractivity changes
96
what happens to a spore during germination?
spore swells, its coat is broken open and a single vegetative cell emerges
97
is the state of dormancy of spores alterable?
yes
98
what is outgrowth?
after germination, cell growth leading up to the formation of the first vegetative cell and before the first cell division is outgrowth
99
what is the structure/cross-section of a bacterial spore?
- spore cytoplasm (core)
- inner membrane surrounds the core
- spore cortex
- spore coat (resistant/multiple layers)
- exosporium (loose outer covering)
100
what are conidia (exospores)? what forms them? what are they vulnerable/resistant to?
- some mycelial bacteria (Actinomycetales) and many filamentous fungi form conidia
- resting spores that are different from endospores
- borne externally by abstriction from the ends of the parent cells (conidiophores)
- are disseminated by the air or other fresh habitats
- not resistant to heat and disinfectants
101
what is pleomorphism of bacteria?
- bacteria of a single strain may show variation in size and shape, or form a proportion of cells that are swollen, spherical, elongated or pear shaped
102
where does pleomorphism occur most readily?
- in certain species (e.g. Streptobacillus moniliformis and Yersinia pestis) in ageing cultures
- species on artificial medium
- species in presence of antagonistic substances eg. penicillin, glycine, lithium chloride, sodium chloride in high concentrations and organic acids at low pH
103
what are involution forms? what is their abnormal shape due to?
abnormal bacterial cells formed by pleomorphism
- some are non-viable, whereas others may grow and revert to the normal form when transferred to a suitable environment
- abnormal shape is due to defective cell wall synthesis and produces a swollen cell, which bursts and lyses
104
how can bacteria be converted into viable spherical bodies?
if bacteria have their cell walls removed or weakened while they're held in a solution of sufficient osmolarity to prevent them taking up water by osmosis, they may escape being lysed and become converted
105
what are free protoplasts?
bacteria that have been converted into viable spherical bodies which have had all cell wall material removed from them
106
what are spheroplasts?
bacteria that have been converted into viable spherical bodies which remain enclosed by an intact, but weakened residual cell wall
107
how can protoplasts and spheroplasts vary in size?
- osmotically sensitive
- vary in size with the osmotic pressure of the suspending medium
- if medium is much diluted, they swell up and perish by lysis
108
what are L-forms of bacteria?
- may arise spontaneously
- cell wall deficient
- difficult to demonstrate as they don't stain with Gram or acid-fast methods and may not propagate in vitro
109
what are the types of groups that microorganisms can be classified into?
1. algae
2. protozoa
3. slime moulds
4. fungi
5. bacteria
6. archaea
7. viruses
110
what types of microorganisms are prokaryotic?
- algae (excluding blue-green algae)
- protozoa
- slime moulds
- fungi
111
what types of microorganisms are eukaryotic?
- bacteria (including organisms of the mycoplasma, rickettsia and chlamydia groups)
- blue-green algae
112
what are viroids?
protein-free fragments of single-stranded circular RNA that cause disease in plants
113
what are prions?
- naturally occurring host cell membrane glycoproteins that undergo conformative changes to an infectious isoform
- causative agents of fatal neurodegenerative disorders
114
what is taxonomy?
- classification, nomenclature and identification of microbes)
- consists of three components: classification, nomenclature and identification
115
what is systematics?
- concerned with evolution, genetics and speciation of organisms
- referred to as phylogenetics
116
how are protozoa, fungi and helminths classified and named?
- according to work from Linnaeus
| - genus, then species, then variant
117
what tests of bacteria are definitive of a genus or species?
universal production of catalase enzyme and cytochrome c, respectively, by Staphylococcus spp. and Pseudomonas aeruginosa
118
what are the taxonomic ranks used in classification of bacteria?
```
Kingdom (Prokaryotae)
Division (Gracilicutes)
Class (Betaproteobacteria)
Order (Burkholderiales)
Family (Burkholderiaceae)
Genus (Burkholderia)
Species (Burkholderia cepacia)
```
119
what are the different methods of classification of bacteria?
- Adansonian or numerical classification
- DNA composition
- DNA homology
- ribosomal RNA sequencing
120
what are subcategories of eukaryotes that are of medical importance?
protozoa and fungi
121
what are examples of protozoa?
sporozoa: plasmodium, isospora, toxoplasma, cryptosporidium
flagellates: giardia, trichomonas, trypanosoma, leishmania
amoebae: entamoeba, naegleria, acanthamoeba
other: babesia, balantidium
122
what are examples of fungi?
mould-like: epiderophyton, trichophyton, microsporum, aspergillus
yeast-like: candida
dimorphic: histoplasma, blastomyces, coccidioides
true yeast: cryptococcus
123
what are examples of actinobacteria?
(High G+C Gram positives)
| actinomyces, streptomyces, corynebacterium, nocardia, mycobacterium, micrococcus
124
what are examples of firmicutes?
gram-positive bacilli: listeria, bacillus, clostridium, lactobacillus, eubacterium
gram-positive cocci: staphylococcus, streptococcus, enterococcus
gram-negative cocci: veillonella, mycoplasma
125
what are examples of proteobacteria?
gram-negative cocci: neisseria, moraxella
gram-negative bacilli: enterobacteria - escherichia, klebsiella, proteus, salmonalla, shigella, yersinia
pseudomonads: pseudomonas, burkholderia, stenotrophomonas, haemophilus, bordetella, brucella, pasteurella
gram-negative curved and spiral bacilli: vibrio, spirillum, campylobacter, helicobacter
126
what are examples of bacteroidetetes?
bacteroides, prevotella
127
what are examples of spirochaetes?
borrelia, treponema, brachyspira, leptospira
128
what are actinobacteria?
- gram-positive bacteria with a high G + C content
- many capable of filamentous growth with true branching which may produce a mycelium
- many do not stain well with the Gram method
- includes mycobacteria which can be recognised with acid fast stains
129
what are firmicutes?
- low G + C Gram-positive bacteria including bacilli
- includes most of the medically significant Gram-positives
- Veillonella and Mycoplasma, which have presumably lost their Gram-positivity, are included
130
what are proteobacteria?
- very large group of Gram-negative bacteria (bacilli and cocci)
- five subdivisions: alpha, beta, gamma, delta and epsilon
- rods, most are motile
- facutatively anaerobic
- some colonise the GI tract
- enterobacteriaceae
131
what are bacteroidetes?
Gram-negative anaerobes
132
what are spirochaetes?
possessing cells with a tight spiral shape and an internal flagellum
133
what are chlamydiae?
strict intracellular parasites
134
what are some categories of actinobacteria?
- actinomyces
- streptomyces
- mycobacterium
- nocardia
- corynebacterium
135
what are features of actinomyces? give examples
gram-positive, non-acid-fast, tend to fragment into short coccal and bacillary forms and not to form conidia; anaerobic
- e.g. Actinomyces israelii
136
what are features of streptomyces? give an example
- vegetative mycelium does not fragment into short forms
- conidia form in chains from aerial hyphae
- e.g. Streptomyces griseus
137
what are features of Mycobacterium? give an example
- acid-fast
- Gram-positive, but does not readily stain by the Gram method
- usually bacillary, rarely branching, make mycolic acids
- e.g. Mycobacterium tuberculosis
138
what are features of Nocardia? give an example
- similar to Actinomyces, but aerobic and mostly acid-fast
- make mycolic acids
- e.g. Nocardia asteroides
139
what are features of Corynebacterium? give an example
- pleiomorphic
- Gram-positive bacilli
- make mycolic acids
- e.g. Corynebacterium diphtheriae
140
what are types of Firmicutes?
- Streptococcus
- Staphylococcus
- Mycoplasma and ureoplasma
- Veillonella
- Gram-positive spore-forming bacilli
- Gram-positive non-sporing bacilli
141
what are features of Streptococcus? give an example
- Gram-positive cocci
- mainly adherent in chains due to successive cell divisions occuring in the same axis (e.g. Streptococcus pyogenes)
- sometimes predominantly diplococcal (e.g. Streptococcus pneumoniae)
142
what are features of Staphylococcus? give an example
- Gram-positive cocci
- mainly adherent in irregular clusters due to successive divisions occurring irregularly in different planes (e.g. Staphylococcus aureus)
143
what does the ZN stain detect?
Mycobacterium/acid-fast bacilli
144
what is LPS/endotoxin made up of?
terminal sugars, O antigen and Lipid A
145
what is between the outer and inner membrane in Gram-negative bacteria?
- lipoprotein
- periplasmic space
- some peptidoglycan
146
what is the goal of spore formation? what do they contain?
- certain harsh conditions; spores are resistant to them
- contain DNA
- wait for better conditions
- resist desiccation
147
what is bacterial environment?
- less than -80 to +80 degrees (120 for spores)
- pH less than 4 to 9
- water/dessication: 2hours to 3 months (>50 years for spores)
- UV light
148
what are the growth conditions and doubling time for viruses, E.coli/S.aureus etc, Mycobacterium tuberculosis, Fungi, Mycobacterium leprae
most viruses: cells; < 1 hour
E.coli, S.aureus etc: broth or solid media; 20-30 mins
Mycobacterium TB: broth or media; 24 hours
Fungi: broth or media; 30 minutes
Mycobacterium leprae: broth or media; 2 weeks
149
what is endotoxin?
component of the outer membrane of bacteria, e.g. LPS in Gram-negative bacteria
150
what is exotoxin?
secreted proteins of Gram-positive and Gram-negative bacteria
151
what is the composition, action, effect of heat, antigenicity, production by, and convertibility to toxoids of exotoxins vs endotoxins?
exotoxins:
- protein
- specific action
- labile (heat effect)
- strong antigenicity
- produced by mostly Gram-positive bacteria
- can convert to toxoid
endotoxins:
- LPS
- non-specific action
- stable (heat effect)
- weak antigenicity
- produced by Gram-negative bacteria
- not convertible to toxoid
152
how does gene transfer occur in bacteria?
transformation e.g. via plasmid
transduction e.g. via phage
conjugation e.g. via sex pili
153
what are obligate intracellular bacteria? what are examples of each?
Rickettsia
- R. rickettsii
- R. prowazekii
- R. conorii
Chlamydria
- C. trachomatis
- C. psittaci
- C. pneumoniae
Coxiella
- C. burnetii
154
what are examples of bacteria that can be cultured on artificial media without a cell wall?
Mollicutes
- Mycoplasma pneumoniae
- M. hominis
- Ureaplasma urealyticum
155
what are categories of bacteria that can be cultured on artificial media with a cell wall?
- growing as single cells
| - growing as filaments
156
what are types of bacteria with a cell wall that grow as filaments? give examples of each
Actinomyces
- A. asraelii
Nocardia
- N. asteroides
Streptomyces
157
what are categories of bacteria growing as single cells that have a cell wall?
- rods
- cocci
- spirochaetes
158
what are types of spirochaetes? give examples of each
Leptospira
- L. icterohaemorrhagiae
Treponema
- T. pallidum
Borrelia
- B. burghdorferi
- B. recurrentis
159
what is the mechanism of action of the Gram stain on Gram-negative bacteria?
decolouriser interacts with the lipids and cells lose their outer LPS membrane and the crystal violet-iodide complexes; appear pink with counterstain
160
what is the mechanism of action of the Gram stain on Gram-positive bacteria?
the decoloriser dehydrates the cell wall and the CV-I complex gets trapped in the multi-layered peptidoglycan
161
what in the Gram stain is used as a decoloriser?
ethanol or acetone
162
what are categories of cocci?
Gram-negative and Gram-positive
163
what are categories of Gram-negative cocci? what are examples of each?
anaerobic: Veillonella
aerobic: Neisseria
- N. meningitidis
- N. gonorrhoeae
164
what are categories of Gram-positive cocci?
aerobic and anerobic
165
what is a type of anaerobic Gram-positive cocci?
Peptostreptococcus
166
what are types of aerobic Gram-positive cocci? give examples for each
Staphylococcus
- S. aureus
- S. epidermidis
Streptococcus
167
what are types of Streptococcus? give examples for each
Beta-haemolytic
- S. pyogenes (A)
- S. agalactiae (B)
Alpha-haemolytic
- S. pneumoniae
- S. oralis
- S. milleri
- S. sanguis
Non-haemolytic
- S. bovis
Enterococcus
- E. faecalis (D)
168
what is involved in the catalase test?
- flavoproteins reduce O2 using superoxide dismutase producing H2O2
- superoxide is converted by catalase to H2O and O2
169
what bacteria are catalase+? which aren't?
- staphylococci are catalase +
- many Gram-negative bacteria and fungi are also catalase +
- streptococci are not catalase +
170
what is the goal of the coagulase test?
- distinguishes S. aureus (coagulase positive) from other staphylococci (coagulase negative)
171
what does coagulase do? how is it detected in the coagulase test?
coagulase activates prothrombin to convert fibrinogen to fibrin
- free coagulase is released and identified by tube coagulase test
- bound coagulase (clumping factor) is identified by a slide test
- negative remains liquid, positive clumps
172
what are examples of coagulase positive and negative staphylococci?
coagulase +: S. aureus
| coagulase -: S. epidermidis
173
what is haemolysis? what does it require? what does it classify?
- the ability of bacteria to break down erythrocytes in blood agar
- requires expression of hemolysin
- useful for classifying streptococci
174
what is alpha haemolysis? what does it look like?
- caused by hydrogen peroxide produced by the bacterium, oxidising hemoglobin and producing the green oxidised derivative methemoglobin
- green/incomplete hemolysis
- agar under the colony is dark and greenish
175
what are examples of bacteria that display alpha haemolysis?
Streptococcus pneumoniae
| Streptococcus viridans
176
what is beta haemolysis? what does it look like? what is it caused by?
- complete haemolysis
- complete lysis of red cells in media around and under colonies
- lightened (yellow) and transparent
- streptolysin, an exotoxin, is the enzyme produced by bacteria that causes the complete lysis of erythrocytes
177
what are types of streptolysins in beta haemolysis?
streprolysin O
- oxygen sensitive cytotoxin secreted by most group A streptococcus and streptococcus dysgalactae
- interacts with cholesterol in membrane of eukaryotic cells
streptolysin S
- oxygen-stable cytotoxin produced by most GAS strains leading to clearing on surface of blood agar
178
what is gamma haemolysis?
- non-haemolytic
- organism doesn't induce haemolysis
- agar under and around the colony is uncharged
179
what are examples of organisms displaying gamma haemolysis?
- enterococcus faecalis
- Staphylococcus saprophyticus
- Staphylococcus epidermidis
180
what organisms produce beta-haemolysis?
S. pyogenes
181
what are examples of mycobacteria?
```
M. tuberculosis
M. leprae
M. avium-intracellulare
M. ulcerans
M. kansasii
```
182
what are categories of Gram-positive rods?
aerobic and anaerobic
183
what are types of anaerobic Gram-positive rods? give examples for each
Clostridium
- C. perfringens
- C. tetani
- C. botulinum
- C. difficile
Proprionibacterium
- P. acnes
184
what are types of aerobic Gram-positive rods? give examples for each
Corynebacterium
- C. diphtheriae
Listeria
- L. monocytogenes
Bacillus
- B. anthracis
- B. cereus
Erysipelothrix
- E. rhusiopathiae
185
what are features of MacConkey agar?
can be used for Gram-negative bacilli
- bile salts inhibit Gram-positive bacteria and inhibit swarming of Gram-negative bacterium Proteus spp.
- crystal violet inhibits some Gram-positive bacteria
- neutral red acts as a pH indicator so bacteria that ferment lactose and release H+ appear pink or red
186
what is CLED media? what is it used for?
Cysteine lactose electrolyte deficient media
- prevents swarming of Proteus mirbilis
- Bromothymol blue is indicator, lactose fermentation causes blue to yellow change, decarboxylation of L-cyteine results in blue colour
- used as media for urinary pathogens
187
what are lactose fermentors (gram-negative aerobes)?
E. coli
Klebsiella pneumoniae
Enterobacter spp.
188
what are slow fermentors (Gram-negative aerobes)?
Serratia spp.
| Citrobacter spp.
189
what are lactose non-fermentors (Gram-negative aerobes)?
```
Salmonella spp.
Shigella spp.
Yesrinia spp.
Proteus spp.
Pseudomonas aeruginosa
```
190
what is the oxidase test used for?
- tests if micro-organism contains a cytochrome oxidase or indophenol oxidase
- utilises a redox indicator e.g. N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD)
- in oxidised state: dark blue/ maroon
- implies organism is able to use oxygen as the terminal electron acceptor
191
what are examples of oxidase+ microorganisms?
pseudomonads, aeromonads, curved rods and Neisseria spp.
192
what does LPS consist of?
- lipid A, the toxic portion of LPS that is anchored in the outer leaflet of the outer membane
- core (R) antigen (core-oligosaccharide), short chain of sugars, some are unique to LPS
- somatic (O) antigen (O polysaccharide), a highly antigenic repeating chain of oligosaccharides
193
why do mycobacteria not stain as Gram-positive?
- mycobacteria have an outer lipid bilayer composed of mycolic acids
- mycoplasmas lack peptidoglycan
194
what are pathogenicity determinants/virulence factors?
any product or strategy that contributes to pathogenicity/virulence
195
what are categories of pathogenicity determinants?
colonisation factors: adhesins, invasins, nutrient acquisition, defence against the host
toxins: usually secretetd proteins (by protein secretion systems) leading to damage and subversion
196
what is the lactose use, lifestyle and motility of Shigella flexneri? (enterobacteria)
- no lactose use
- primate pathogen
- not motile
197
what is the lactose use, lifestyle and motility of Escherichia coli? (enterobacteria)
- does use lactose
- mammalian commensal and pathogen
- is motile
198
what is the lactose use, lifestyle and motility of Salmonella enterica? (enterobacteria)
- no lactose use
- mammalian pathogen
- is motile
199
what are cell surface antigens of Gram-negative bacteria?
```
H antigen (flagella)
O (somatic) antigen (LPS
K antigen (exopolysaccharide capsule)
```
200
what are principal infections caused by pathogenic Escherichia coli strains?
- wound infections (surgical)
- UTIs
- gastroenteritis
- travellers' diarrhoea
- bacteraemia (sometimes leading to sepsis)
- meningitis
201
what is the mechanism of ETEC heat labile enterotoxin?
- stimulates heat labile enterotoxin
- stimulates Gs, activates adenylate cyclase, increases cAMP, activates PKA and activates the CFTR
- activates CFTR; transport of Cl-/H2O out of cell at apical surface
202
what is the mechanism of ETEC heat stable enterotoxins?
- activation of guanylate cyclase
| - increased cGMP, activation of cGMP-dependent protein kinase, which activates CFTR
203
what is ETEC, PEC, and EHEC?
enterotoxigenic
enteropathogenic
enterohaemorrhagic
204
what is EIEC, EAEC and UPEC?
enteroinvasive
enteroaggregative
uropathogenic
205
why are some E. coli strains pathogenic?
- several pathovars (distinct pathogenic strategies)
- common core genome
- acquisition of pathogenicity genes (lateral gene transfer)
206
what are the effects of EHEC/EPEC induced pedestal formation?
diarrhoea symptoms caused by disruption of tight junctions and effects on ion secretion
207
what is the process of EHEC/EPEC-induced pedestal formation?
1. initial adherence by bundle-forming pili
2. T3SS (syringe-like protein secretion system) activity - effector secretion. Actin microfilament depolymerisation, microvilli effacement
- injection of Tir (translocated intimin receptor)
3. intimin-dependent signalling
- actin nucleation, pedestal formation, intimate attachement
- intimin is a bacterial adherence protein
208
what is the pathogenesis of GI infection caused by EPEC in the SI?
destruction of microvilli and entrance into cells
209
what is the pathogenesis of GI infection caused by ETEC in SI?
heat labile enterotoxin and heat stabile enterotoxin
210
what is the pathogenesis of infection caused by EHEC, EIEC and EAEC in the colon?
shiga-like toxin
| heat stable enterotoxin like haemolysin
211
what are the different species of shigella?
S. dysenteriae
S. flexneri
S. boydii
S. sonnei
212
what does Shigella cause?
- severe bloody diarrhoea
- frequent passage of stools (>30/day)
- small volume, pus and blood, prostrating cramps, pain in straining, fever
- self limiting in adults
213
what is the pathogenesis of Shigella infection? how is it spread?
- acid-tolerant
- person-to-person, contaminated water and food
- entry through colonic M cells (antigen sampling, overlie lymphoid follicles)
- induced uptake
214
what happens in invasion of the colonic mucosa by Shigella?
- entry through M cells on enterocyte apical surface
- shigella passes through tight junctions and spread through the cells
- apoptotic macrophages
- translocating PMNs to the site of infection
215
what is the shiga toxin?
- catalytic subunit (glycosidase)
| - receptor binding subunits
216
what is the action of the Shiga toxin?
- cleaves N-glycosidic bond of adenosine residue in 28S rRNA (60S subunit)
- blocks EF-1 and EF-2 binding -> protein synthesis inhibited
217
what complication does the Shiga toxin cause?
systemic absorption of Shiga toxin -> targets kidney -> HUS (microvascular thrombosis in kidneys -> kidney failure
218
what are the main clinically relevant Gram-negative bacteria?
1. Escherichia coli
2. Shigella
3. Salmonella
219
what are the species of Salmonella?
S. enterica - responsible for salmonellosis
S. bongori - rare (contact with reptiles)
220
what are the three salmonellosis caused by S. enterica?
1. gastroenteritis/entercolitis (serovars Enteritidis and Typhimurium)
2. Enteric fever - typhoid (serovars Typhi and Paratyphi)
3. Bacteraemia (serovars Cholerasuis and Dublin)
221
what is the pathogenesis of salmonellosis?
- invasion of gut epithelium (SI)
- intestinal secretory and inflammatory response (serovars Enteritidis and Typhimurium)
- transcytosed to basolateral membrane
- enters submucasal Ms
- intracellular survival/replication
222
how is salmonella spread?
ingestion of contaminated food/water
223
how does salmonella lead to systemic infection?
dissemination within Ms (serovar Typhi)
224
what are the steps in pathogenesis of gastroenteritis caused by salmonellosis?
1. bacterial-mediated endocytosis
2. induction of chemokine release
3. neutrophil recruitment and migration
4. neutrophil-induced tissue injury
5. fluid and electrolyte loss -> diarrhoea
- > inflammation/necrosis of the gut
- no systemic spread
225
what is the pathogenesis of enteric fever caused salmonellosis
1. bacterial-mediated endocytosis
2. transcytosis to basolateral membrane
3. survival in M -> systemic spread
- > initially, little damage to gut mucosa
- migration to reticuloendothelial organs via lymphatics and blood
226
what are the effects of typhoid (enteric) fever?
ingestion of S. Typhi -> small intestine -> inflammation and ulcertation of Peyer's patches -> diarrhoea: haemorrhage or perforation (1-3% of cases)
multiplication in macrophages -> secondary bacteraemia (septicaemia) -> fever: kidney and other organs affected
gall bladder -> carrier state (1 year to rest of life)
227
how is typhoid (enteric) fever dealt with by the body?
ingestion -> small intestine -> mesenteric lymph nodes -> transient bacteraemia (thoracic duct - enter bloodstream) -> multiplication in macrophages in liver, spleen and bone marrow -> gall bladder (from liver) -> small intestine (via bile)
228
what is the incubation period of typoid (enteric) fever?
1-3 weeks; asymptomatic
229
what is Proteus mirabilis?
differentiates into an elongated hyperflagellated form known as a swarmer cell -> surface motility
- normally flagellated form is the swimmer cell -> motility in liquid
230
what can Proteus mirabilis lead to? what is its virulence factor?
- opportunistic
- UTI -> pyelonephritis, septicaemia
- virulence factor: urease (increased pH) -> kidney stones
231
what is Klebsiella pneumoniae? what does it do?
- environmental
- opportunistic, nosocomial infections (neonates, elderly, compromised)
- colonisation of GIT (normal) and oropharynx (less frequent) is benign
- can lead to UT, pneumonia, surgical wound infections, bacteraemia - sepsis
- MDR (resistant to carbapenems)
232
what is Enterobacter (E. cloacae, E. aerogenes)? what does it lead to?
- opportunic, nosocomial outbreaks
- infections in lungs, urinary tract, abdominal cavity, IV devises, sepsis
- spread from endogenous gut flora, can survive on skin, patient-to-patient transmission
- cephalosporin resistant forms
233
what is Yersinia spp.? what does it lead to?
- primary pathogen
- Y. enterocolitica: localised to ileum; gastroenteritis
- Y. pestis: systemic; bubonic plague
234
what is Vibrio cholerae? what does it lead to?
- facultative anaerobe
- curved rods with a single polar flagellum
- saline environments: commensal to planktonic crustaceans e.g. copepods
- ingestion by shellfish, contamination of drinking water due to flooding of coastal areas or poor sanitation
235
what is the incubation time for Vibrio cholerae?
hours to 5 days (multiplies in small intestine)
236
what are the virulence determinants for Vibrio cholerae?
- TCP pili: required for colonisation
| - cholera toxin (A and B subunits)
237
what is the action of cholera toxin?
1. binds a ganglioside (glycolipid) receptor (B subunits)
2. A subunit ADP-ribosylates Gs -> locked in ON state
3. uncontrolled cAMP production
4. protein kinases activated
5. CFTR ion transporter activity modified (loss of Cl- and Na+)
6. massive loss of H2O
238
what is Pseudomonas aeruginosa? what does it lead to?
- ubiquitous, free-living, aerobe
- motile: single polar flagellum
- opportunistic (serious cause of nosocomial infections)
- multiple antibiotic resistance
- very difficult to treat
239
what are types of acute infections caused by P. aeruginosa?
localised
- burns/surgical wounds
- UTI (catheters)
- keratitis
systemic (bacteraemic -> sepsis)
- neutropenic patients (leukaemia, chemotherapy, AIDS)
```
ICU patients (ventilators)
- leading cause of nosocomial pneumonia
```
240
what is a type of chronic infection caused by P. aeuginosa?
CF
241
what are P. aeruginosa virulence determinants?
multiple toxins: main virulence determinants in acute infections
- exoenzyme S and U interfer with cell signalling
- exotoxin A, elastase, phospholipase cause cell death/damage
- cyanide
CF: copious amounts of exopolysaccharide alginate is a virulence factor
242
what is Haemophilus influenzae? how is it carried?
- exclusively human parasite
- nasopharyngeal carriage in 25-80% of the population (non-capsulate)
- transient carriage of capsulate strains in 5-10%
243
what can Haemophilus influenzae lead to?
opportunistic infections seen mainly in young children and adult smokers
- meningitis (< age 5 years), 5-10% of adult cases
- bronchopneumonia
- epiglottitis, sinusitis, otitis media
- bacteraemia (often associated with pharyngitis)
- pneumonia in CF, COPD, HIV patients
244
what is chocolate agar?
blood agar which has been heated to 80 degrees to allow release of haem and NAD by erythrocytes. colour of the agar is brown rather than red
245
what are virulence determinants of H. influenzae?
capsule - invasive strains are encapsulated
- can penetrate nasopharyngeal epithelium
- resistance to phagocytosis and complement system
- capsule allows typing into 6 serogroups (a-f)
LPS
- inflammation
- complement resistance
246
what is NTHi?
non-typeable H. influenzae
- commensals and upper respiratory tract pathogens are non-capsulate
- capsule allows typing into 6 serogroups (a-f)
- type b strains are main cause of meningitis
247
what is Legionella pneumophilia? what does it cause?
- discovered 1976
- Lesionnaires' disease -> severe inflammatory pneumonia
- affects the immunocompromised
- severe (15-20% mortality)
248
how does Legionella pneumophilia grow?
- fastidious: culture on charcoal agar
- man-made aquatic environments
- replicate within freshwater protozoa - intracellular parasite of amoeba
- can infect alveolar macrophages
249
what is Bordetella pertussis? what does it cause?
- pertussis (whooping cough)
- B. parapertussis causes mild pharyngitis
- short (sometimes oval) rods (coccobacilli)
- fastidios, non-invasive, highly contagious (aerosol transmission)
- obligate human pathogen
250
what is the mechanism of action of B. pertussis?
- predilection for ciliated epithelia
| - binds to respiratory epithelial cells
251
what are the toxins in B. pertussis? how do they act?
Pertussis toxin
- S1 subunit ADP-ribosylates Gi -> locked in OFF state
- PT -> increased cAMP
adenylate cyclase-haemolysin toxin (CyaA)
- hypersynthesis of cAMP -> suppression of innate immune functions
252
what is Neisseria? where is it present?
- non-flagellated diplococci
- fastidious
- obligate human pathogen
- present in PMNs of CSF (N.m) or urethral discharge (N.g.) during infection
253
what are the two medically important forms of Neisseria?
N. meningitidis
| N. gonorrhoeae
254
what is the incidence of N. meningitidis? how does it spread?
- nasopharynx of 5-10% of the population (asymptomatic)
- 20-90% during outbreaks
- person-to-person (aerosol) transmission (universities, barracks, Haj)
255
what is the pathogenesis of N. meningitidis?
- crosses nasopharyngeal epithelium and enters bloodstream in small proportion of colonised individuals
- > low level bacteraemia (asymptomatic) or septicaemia (sepsis)
- > meningitis: invasion of the meninges; bacteria enter CSF of subarachnoid space from blood stream after crossing BBB
- very high mortality of septicaemic form if not treated
256
what are the virulence determinants of N. meningitidis?
capsule (serogroup B in 90% of cases)
-> antiphagocytic
noncapsulated N.m. only found in nasopharynx - not pathogenic
LPS (membrane blebs)
- > cytokine cascade
- > sepsis
257
what are fungi? what are their characteristics?
- large, diverse group of heterotrophic organisms
- mostly found as saprobes in the soil and on decomposing organic matter
- eukaryotic
- have a range of internal membrane systems, membrane bound organelles, and a well defined cell wall
258
what is the fungal cell wall made up of?
composed largely of polysaccharides (glucan, mannan) and chitin
259
what are the three main groups that fungi can be divided into?
1. moulds (multicellular filamentous fungi)
2. yeasts
3. dimorphic fungi
260
what are moulds composed of? how do they reproduce? do they produce spores?
- multicellular filamentous fungi
- composed of branching filaments, termed hypae, that grow by apical extension ot form an intertwined mass (mycelium)
- hyphae often have regular cross walls
- reproduce by asexual spore production (mitosis) or by sexual reproduction (meiosis)
261
what are hyphae (in fungi)?
branching filaments that grow by apical extension to form an intertwined mass (mycelium)
262
what is a mycelium (in fungi)?
an intertwined mass formed by growth of hyphae by apical extension
263
what are yeasts? how do they reproduce?
- predominantly unicellular and oval or round in shape
- most propagate by an asexual process called budding where the cell develops a protuberance, which enlarges and eventually separates from the parent cell
- some produce chains of elongated cells (pseudohyphae)
- some reproduce by fission
264
what is budding (in fungi)?
asexual process used by yeasts where the cell develops a protuberance, which enlarges and eventually separates from the parent cell
265
what are pseudohyphae (in fungi)?
- produced by yeasts
| - chains of elongated cells that resemble the hyphae of moulds
266
what are dimorphic fungi?
group of fungi that are capable of changing their growth to either a mycelial or yeast phase, depending on growth conditions
267
what is the division of the fungal kingdom?
currently divided into seven phyla; includes the Ascomycota, Basidiomycota and Glomeromycota
268
how are yeasts identified?
primarily according to their ability to ferment sugars and to assimilate carbon and nitrogen compounds
269
what is mycosis?
disease caused by fungal pathogens
270
how many fungal pathogens cause disease in humans?
less than 500
271
how do dimorphic fungi change according to conditions?
usually change from a multicellular mould form in the natural environment to a budding single celled yeast form when causing infection
272
how can dimorphic fungi change be induced in a laboratory?
tissue form can be induced by culture at 37degrees on rich media e.g. blood agar
mould form develops when incubated at a lower temp (25-30degrees) on a less rich medium e.g. Sabouraud dextrose agar
273
what are examples of fungi that can establish an infection in all exposed individuals?
Histoplasma capsulatum
| Blastomyces dermatitidis
274
what are examples of fungi that are opportunist pathogens?
Candida
| Aspergillus
275
how can fungi cause serious and sometimes fatal toxic effects in humans?
- ingestion of poisonous toadstools
- consumption of mouldy food that contains toxic secondary metabolites (mycotoxins)
- inhalation of fungal spores may lead to allergic disease of the airways
276
what are types of fungal infection?
- superficial mycoses
- subcutaneous mycoses
- systemic mycoses
277
what are superficial mycoses?
diseases of the skin, hair, nail and mucous membranes
278
what are examples of superficial mycoses?
- dermatophytosis (ringworm)
| - yeast infections
279
what is dermatophytosis?
- ringworm
- superficial mycosis
- complex of diseases affecting the outermost keratinised tissues of hair, nail and the stratum corneum of the skin
- caused by mould fungi: dermatophytes, which can ingest keratin
280
what do dermatophytes ingest?
keratin
281
what are yeast infections? what are they usually caused by?
- superficial mycosis
- affect the skin, nail and mucous membranes of the mouth and vagina
- usually caused by the Candida species, esp. Candida albicans
- infection is generally endogenous in origin but genital infection can be transmitted sexually
282
what can Malassezia furfur cause?
- skin commensal
| - infection of skin called pityriasis versicolor
283
what are subcutaneous mycoses? where do they usually occur? what causes them?
- mycoses of the dermis, subcutaneous tissues and adjacent bones that show localised spread
- occur mainly in the tropics and subtropics
- caused by traumatic inoculation of saprobic fungi from soil or vegetation into the subcutaneous tissue
284
what are the principal subcutaneous mycoses?
- mycetoma
- chromoblastomycosis
- sporotrichosis
285
what are systemic mycoses? what groups can the causative organisms be divided into?
- deep-seated fungal infections result from the inhalation of air-borne spores produced by casual moulds present as saprobes in the environment
- initially: pulmonary infection
- true pathogens and opportunistic pathogens
286
what are examples of true pathogens that cause systemic mycoses?
mostly dimorphic fungi; infections occur mainly in Americas
287
what are the principle systemic mycoses? what are they caused by?
- blastomycosis (Blastomyces dermatitidis)
- coccidioidomycosis (Coccidioides immitis and C. posadasii)
- histoplasmosis (H. capsulatum)
- paracoccidioidomycosis (Paracoccidioides brasiliensis)
288
what is the incidence of fungal mycoses? what are groups commonly affected?
- dermatophytosis of the foot (athletes foot) occurs most commonly in people using communal bathing facilities
- animal dermatophytosis occurs in farmers, vets, people who work with animals
- agricultural workers in warm climates may contract subcutaneous infections following minor injuries from vegetation
- AIDS is associated with increased rate of opportunistic fungal infections
- increased urban development, land use, tourism
289
what does laboratory diagnosis of fungal infections depend on?
- recognition of the pathogen in tissue by microscopy
- isolation of the causal fungus in culture
- serological tests
- detection of fungal DNA by PCR
290
what are the most common tests for fungal antibodies?
- immunodiffusion
- countercurrent immuno-electrophoresis
- whole cell agglutination
- complement fixation
- enzyme-linked immunosorbent assay (ELISA)
291
what are characteristics of treatment for fungal infections?
- fungi and humans are both eukaryotes
- most substances that kill or inhibit fungal pathogens are also toxic to the host
- most exploit differences in the sterol composition in cell membranes
- echinocandins interfere with beta-glucan synthesis in the fungal cell wall
292
what are examples of administration of drugs for fungal infection?
- Amphotericin B and the echinocandins are given parenterally due to poor absorption from the GI tract
- fluconazole, itraconazole, posaconazole, voriconazole and flucytosine are available for oral and/or parenteral administration
- terbinafine and griseofulvin administered orally
-
293
what is dermatophytosis caused by? what are the three genera?
20 species of fungi
| - trichophyton, microsporum and epidermophyton; classified based on morphology of macroconidia
294
what types of asexual spores do dermatophytes produce?
- multicelled macroconidia
| - single celled microconidia
295
how are dermatophytic infections spread? how long can they stay viable?
- spread by direct or indirect contact with infected human/animal
- infective particle is usually a fragment of keratin containing viable fungus
- indirect transfer may occur via pool floors, brushes, towels etc
- viable for long time
- abnormality of epidermis probably necessary for infection
296
what are clinical features of dermatophytosis?
- dry scaling or hyperkeratosis
- irritation, erythema, oedema, vesiculation
- spreading annular lesions with raised inflammatory border are produced in skin
- discoloured, thickened, raised and friable in nail infections
- scaling and hair loss
- id reaction
297
what is superficial candidosis?
involve the skin, nails and mucous membranes of the mouth and vagina
298
what is superficial candidosis caused by?
```
C. albicans
C. glabrata
C. parapsilosis
C. tropicalis
C. krusei
C. guilliermondii
```
299
what is the growth of the Candida species like?
- on Sabouraud dextrose agar, they grow predominantly in the yeast phase as round or oval cells, 3-8 mm in diameter
- mixture of yeast cells, pseudohyphae and true hyphae is found in vivo and under micro-aerophilic growth conditions on nutritionally poor media
- C. glabrata doesn't from hyphae or pseudohyphae
300
when does yeast overgrowth and infection occur?
when the normal microbial flora of the body is altered or when host resistance to infection is lowered by disease
301
how much of the population has Candida species?
- found in small numbers in the commensal flora (mouth, GI tract, vagina, skin) of about 20% of the normal population
- carriage rate tends to increase with age and is higher in the vagina during pregnancy
- commensal yeasts are more prevalent among patients in hospital
302
how can superficial candidosis spread?
- often derived from an individual's own endogenous resevoir
- transmission from person to person can occur
- neonatal oral candidosis is more common in infants born of mothers with vaginal candidosis
- hands of healthcare workers are source of neonatal infection
303
what are some defenses against Candida infection?
- individuals colonised with Candida species have non-specific and immunological defenses to prevent infection
- non-specific inhibitory factors include inhibitors in serum, e.g. unsaturated transferrin and epithelial proliferation
- specific defence depends on development of active T-cell mediated immunity
304
what are some general and local predisposing factors to developing oropharyngeal candidosis?
- debilitated and immunosuppressed individuals, e.g. diabetes mellitus, stem cell transplant recipients and those with HIV
- xerostomia and trauma from unhygienic or ill-fitting dentures
- local tissue damage
- moist, occluded, macerated tissue
305
what are clinical features of mucosal superficial candidosis infection?
- discrete white patches develop on mucosal surface, may become confluent and form a curd-like pseudomembrane
- oropharyngeal: white flecks appear on buccal mucosa, tongue and hard and soft palate. surrounding mucosa is red and sore.
- lesions in occluded area under denture
- painful infection of tongue in antibiotic therapy
- chronic infection with extensive leucoplakia and infection of angles of mouth
- vaginal candidosis: itching, soreness and non-homogenous white discharge and white legions
306
what are clinical features of skin and nail superficial candidosis infection?
- lesions develop in warm, moist sites e.g. axillae, groin and submammary folds
- infection of finger webs, nail folds and nails associated with frequent immersion of hands in water
307
what are clinical features of chronic mucocutaneous candidosis infection?
- becomes apparant in childhood
- persistent, sometimes granulomatous, infection of mouth, scalp, hands, feet and nails
- disfiguring hyperkertotic lesions develop on the scalp and face
- subtle defects in lymphocyte function
308
what is pityriasis versicolor?
- common, mild and often recurrent infection of the stratum corneum
- produces a patchy discolouration of the skin caused by the lipophilic yeasts of the genus Malassezia
309
what is pityriasis versicolor caused by?
lipophilic yeasts of the genus Malassezia
- require lipids for growth and special media containing Tween and lipid supplements have been developed
- on normal skin and in dandruff and seborrhoeic dermatitis, Malassezia occurs as an oval or bottle shaped yeast, which produces buds on a broad base
- in pityriasis versicolor it produces round yeast cells and short hyphae
310
how does infection by Malassezia species often occur? where is it common?
- common members of normal skin flora
- most infections are endogenous
- incidence of skin colonisation is 25% in children to almost 100% in adolescents/adults
- disease probably related to host and environmental factors
- common in hot, humid tropical climates
311
what are clinical features of Pityriasis versicolor?
- small patches of well demarcated, non-inflammatory scaling usually present on the upper trunk or neck
- patches may be hypo/hyperpigmented, depending on degree of pigmentation of surrounding skin
- lesions tend to spread and coalesce
312
what can cause otomycosis? how can it be treated?
- fungal ear infection
- 10-20% of chronic ear infections are due to fungi
- worldwide distribution but more common in warm climates
- topical antibiotics and steroids are predisposing factors
- Aspergillus, esp. A. niger
- treatment with topical antifungals; relapse is common
313
what is mycotic keratitis? how can it be treated?
- fungal infections of the cornea usually follow traumatic implantation of spores
- topical antibodies and steroids are predisposing factors
- hot climates
- caused by common saprophytic moulds, esp. Aspergillus and Fusarium species
- surgical debridement of the infected tissue, discontinuation of topical corticosteroids, antifungal drugs, natamycin (topical) or azole (oral)
314
what is mycetoma?
- subcutaneous infection
- chronic granulomatous infection of skin, subcutaneous tissues, fascia and bone
- often affects foot or hand
315
what can mycetoma be caused by?
- different actinomycetes (actinomycetoma) or moulds (eumycetoma)
- traumatic inoculation of the organism into subcutaneous tissue from soil or vegetation, usually on thorns or wood splinters
- agricultural workers
316
what organisms are involved in mycetoma?
```
Madurella
Leptosphaeria
Acremonium
Pseudallescheria
Actinomadura
Nocardia
Streptomyces
```
- form colonies (grains) 0.5-2mm in diameter in the host tissues
- colour depends on organism
317
what are clinical features of mycetoma?
- localised swollen lesions that develop multiple draining sinuses on the limbs
- long period between initial infection and formation of the characteristic lesions
- spread from site of origin is unusual but can happen
318
what is chromoblastomycosis? where is it commonly seen?
- chromomycosis
- chronic, localised infection of the skin and subcutaneous tissues, characterised by slow-growing verrucous lesions usually involving the limbs
- mainly in tropics, in Central and South America and Madagascar
319
what are the principal causes of chromoblastomycosis?
Fonsecaea pedrosoi
F. compacta
Phialophora verrucosa
Cladophialophora carrionii
- infection follows traumatic inoculation of the organism into the skin or subcutaneous tissue
- outdoor occumpations
320
what is sporotrichosis?
- chronic, pyogenic, granulomatous infection of the skin and subcutaneous tissues that remain localised or show lymphatic spread
- rare in Europe
321
what is sporotrichosis caused by?
- Sporothrix schenckii
- found in soil and plant materials
- dimorphic fungus; develops as a mould at 25-30 with septate hyphae; yeast phase forms in tissue and in culture at 37, is composed of spherical or cigar shaped cells
- minor trauma mostly in adults
- gardeners and florists
322
what are clinical features of sporotrichosis?
- nodular, ulcerating disease of the skin and subcutaneous tissues
- spread along local lymphatic channels
- primary lesion is usually on hand with secondary lesions extending up the arm
- may disseminate to bones, joints, lungs, CNS; usually in debilitated/immunosuppressed individuals
323
what is phaeohyphomycosis? how is it treated?
general term used to describe solitary subcutaneous lesions caused by any brown pigmented mould
- if untreated, they slowly increase in size to form a painless abscess
- diagnosis made at surgery
- treatment by excision
324
what is coccidioidomycosis?
- systemic mycosis
325
what is the difference between yeast and mould?
- yeasts are small single celld organisms that divide by budding
- moulds form multicellular hyphae and spores
- dimorphic fungi exist as both yeasts and mould and switch when conditions suit
326
what are types of people affected by invasive/life threatening fungal disease? what are examples?
immunocompromised hosts
- Candida
- invasive aspergillosis
- pneymocystis
- cryptococcosis
- mucormycosis
post-surgical patients
- intraabdominal infection (Candida)
healthy hosts
- fungal asthma
- travel associated fungal infections (dimorphic fungi)
- post influenza aspergillosis
327
what methods are used to diagnose fungal disease?
- microscopy and histology
- culture
- molecular methods and serology
328
what is onychomycosis?
fungal nail infection
329
what fungi can cause onychomycosis?
Trichophyton spp.
Epidemophyton spp.
Microsporum spp.
Non-dermatophytes:
- Candida spp
- Fusarium spp.
- Scopulariopsis brevicaulis
- Scytalidium hyalinum
- Aspergillus
330
what are differential diagnoses of onychomycosis?
- psoriasis
- lichen planus
- trauma
- eczema
- yellow nail syndrome
- periungual squamous cell carcinoma/Bowens disease
- alopecia areata
331
what is the diagnosis and treatment of onychomycosis?
- difficult to treat and it is desirable to confirm the diagnosis
- diagnosis by microscopy and culture of nail clippings/scrapings
- usual treatments are terbinafine or itraconazole
332
how are nail samples collected?
1: proximal clippings; material from underside of plate; skin scrapings from any Tinea
2: surface scrape of loose material
3: scrape away normal nail plate then curette proximal tissue or biopsy
333
what is mucosal candidosis associated with?
- immunocompromised patients
- diabetes
- antibiotics
- dentures
- pregnancy
- poorly ventilated underwear
334
what is mucosal candidosis treated with?
topical antifungals or oral fluconazole
- resistance
- usually a clinical diagnosis but culture in refractory cases
335
how is pneumocystis pneumonia diagnosed and treated?
- gold standard diagnostic test is PCR of induced sputum or BAL
- treatment with co-trimoxazole
336
what is (1,3)-beta-D glucan?
- cell wall component of many fungi including common ascomycetous pathogens and Pneumocystis; not zygomycete or basidiomycetes
- non-specific for individual fungi
- released into serum during invasive infection
337
how is selective toxicity used in treating fungal disease?
- antimicrobial drug therapy relies on identifying molecules with selective toxicity for organism targets
- target does not exist in humans
- target is significantly different to human analogue
- drug is concentrated in organism cell with respect to humans
- increased permeability to compound
- modification of compound in organism/human cellular environment
- human cells are rescued from toxicity by alternative metabolic pathways
338
what is the aim of antimicrobial drug therapy?
to achieve inhibitory levels of agent at the site of infection without host cell toxicity
339
what are fungal cells like compared to human cells?
- DNA/RNA synthesis, protein synthesis; similar to mammalian
- cell wall contains mannoproteins, B1,3 glucan, B1,6 glucan and chitin; doesn't exist in humans
- plasma membrane contains ergosterol; human cell membrane contains cholesterol, not ergosterol
340
what is the fungal cell wall and plasma membrane made of?
cell wall
- mannoproteins
- B1,3 glucan
- B1,6 glucan
- chitin
plasma membrane
- ergosterol
341
how can drugs target different parts of the fungal cell?
- flucytosine targets DNA/RNA synthesis, protein synthesis
- echinocandins target the cell wall
- amphotericin, azoles and terbinafine target the plasma membrane
342
what is the pathway of ergosterol synthesis?
Acetyl CoA -> Farnesyl pyrophosphate -> Squalene -> Squalene epoxide -> lanosterol -> 4,4-dimethylcholesta-8,14,24-trienol -> 4,4-dimethylzymosterol -> fecosterol -> episterol -> ergosta-5,7,24(28)-trienol -> ergosterol
343
what drugs affect which parts of the ergosterol synthetic pathway?
- allylamines affect squalene -> squalene epoxide
- azoles affect lanosterol -> 4,4-dimethylcholesta-8,14,24-trienol
- morpholines affect dimethylcholesta-8,14,24-trienol -> 4,4-dimethylzymosterol and fecosterol -> episterol
344
what is an example of an allylamine?
terbafine
345
what is the action of terbafine? how is it distributed? what is it used to treat?
- reversible inhibition of squalene epoxidase
- fungicidal
- well absorbed but extensive first pass metabolism; bioavailability 45%
- distributes extensively to poorly perfused sites including skin and nail beds
- used to treat dermatophytes
- well tolerated
346
what is the action of azoles?
- dose dependent inhibitors of 14alpha-sterol demethylase (lanosterol demethylase)
- other secondary targets in synthetic pathway also inhibited by triazoles
- fungistatic
- newer azoles have increased spectrum of activity
347
what are examples of azoles?
- clotrimazole
- miconazole
- ketoconazole
- itraconazole
- fluconazole
- voriconazole
- posaconazole
348
how is the spectrum of activity of azoles determined?
by degree of inhibition of 14alpha-demethylase and secondary targets
349
what is fluconazole used to treat?
Candida, Cryptococcus
350
what is Itraconazole used to treat?
degree of mould activity - Aspergillus, Fusarium and dimorphics (often used for dermatophytes)
351
what is Voriconazole used to treat?
improved activity against moulds - treatment of choice for invasive aspergillosis
352
what are posaconazole and isvuconazole used to treat?
activity against zygomycetes
353
what are some adverse effects of azoles?
- relatively safe
- all associated with transaminitis and GI SEs
- drug interactions due to CYP metabolism
- voriconazole associated with reversible visual disturbance in 30%
- photosensitivity in 1-2% of patients receiving voriconazole
354
what are the mechanisms of azole resistance by Candida?
target site modification
- mutations in ERG11 gene
- itraconazole and posaconazole affected less than fluconazole and voriconazole
increased expression of ERG11
efflux
- may be fluconazole specific or affect other drugs in this class
355
what are species of Candida that show intrinsic reduced susceptibility/resistance to azoles?
C. glabrata, C. krusei
356
what are polyenes? give examples
amphoteric molecules
| - amphotericin B, nystatin and natamycin
357
what are polyene antimycotics?
target fungi
- bind to ergosterol in the fungal cell membrane and weaken it, causing leakage of K+ and Na+ ions, which may lead to cell death
358
what is the structure of polyene antimycotics?
- large ring of atoms containing multiple conjugated carbon-carbon double bonds on one side of the ring (hydrophobic) and multiple hydroxyl groups on the other side (hydrophilic)
- often have a d-mycosamine group bonded
359
how can polyene antimycotics cause toxicity?
affinity for cholesterol in mammalian membranes
- nephrotoxicity: dose dependent, usually reversible
- distal renal tubular acidosis (hypokalaemia)
- hyperkalaemia with rapid infusion (cellular damage)
- infusion related chills/rigors/hypotension and acute anaphylactoid reactions
360
what is the action of echinocandins? what can cause resistance to them?
how are they administered?
- inhibitors of 1,3 beta glucan synthase
- fungicidal to susceptible yeasts, fungistatic to moulds with activity at hyphal tip
- genera without large amounts of 1,3 beta glucan are intrinsically resistant
- IV only
- few side effects/interactions
- treatment of choice in severe/resistant disease
361
when can fungi cause severe disease?
immunocompromised patients
362
why can fungi be challenging to diagnose?
specific tests or specimen handling is required and culture is often slow and insensitive
363
what is coccidomycosis? what is it caused by?
- systemic mycosis
- infection of the lungs
- caused by Coccidioides immitis and C. posadasii (dimorphic fungi)
364
how does Coccidioides grow?
grows as mould
- produces large numbers of barrel-shaped arthroconidia which are easily dispersed in wind currents
- in longs the arthroconidia form spherules containing multiple endospores
365
how is Coccidioidomycosis infection acquired? what is its incubation period?
- inhalation
| - 1-3 weeks
366
what is a risk factor for Coccidioidomycosis?
- environmental exposure
- ground-disturbing activities, e.g. construction and archaeological excavation
- natural events producing dust clouds
- black, Asian, Filipino ethnicity, pregnant women
367
what are clinical features of Coccidioidomycosis?
- wide spectrum of disease
- transient pulmonary infection that resolves without treatment
- chronic pulmonary infection
- more widespread disseminated disease
- more sites can be involved
- meningitis (without therapy) is almost always fatal
368
what is the treatment for Coccidioidomycosis?
- IV amphotericin B
- oral fluconazole used to treat patients with skin, soft tissue, bone or joint infections
- itraconazole is effective, but less tolerated
369
what is Histoplasmosis? what is it caused by?
- systemic mycosis
| - caused by H. capsulatum, a dimorphic fungus found in soil enriched with droppings of birds and bats
370
what causes Histoplasmosis infection? what is the incubation period?
- inhalation of spores
| - 1-3 weeks
371
what are the risk factors for Histoplasmosis?
- environmental exposure
- exposure to sites contaminated with H. capsulatum
- activities that disturb accumulations of bird or bat guano
- most serious disseminated forms of the disease are more common among individuals with underlying cell-mediated immunologicla deficiencies
372
what are clinical features of Histoplasmosis?
- wide spectrum of disease
- ranges from transient pulmonary infection that subsides without treatment, to chronic pulmonary infection, to widespread disseminated disease
- higher levels of exposure lead to acute symptomatic and severe flu like illness
- disseminated disease can lead to an acute illness that's fatal if left untreated, to a chronic infection affecting many sites
373
what is the treatment of Histoplasmosis?
- IV amphotericin B for more severe forms of disseminated histoplasmosis
- itraconazole used in non-immunocompromised patients with milder forms of disseminated disease
374
what is Blastomycosis? what is it caused by?
- systemic mycosis
- B. dermatitidis
- dimorphic soil inhabiting fungus
375
how does B. dermatitidis grow?
- in culture at 25-30 it grows as a mould with a septate mycelium
- colony varies in texture from floccose to smooth and from white to brown in colour
- asexual conidia are produced on lateral hyphal branches of variable length; oval or pear shaped conidia
- in tissue and in culture at 37 the fungus grows as a large round yeast that produces broad based buds
376
what is the epidemiology of Blastomycosis?
- infection results from inhalation of spores
- incubation period is 4-6 weeks
- more commonly seen in adults than in children
- outdoor occupation/recreational interest
377
what are examples of systemic mycoses?
- coccidioidomycosis
- histoplasmosis
- blastomycosis
- paracoccidioidomycosis
- aspergillosis
- invasive candidosis
- cryptococcosis
- murormycosis
- pneumocystosis
378
what is a virion?
the basic infectious particle of a virus
| - in simplest viruses, this consists of nucleic acid and a surrounding coat of protein (capsid)
379
what may some viruses be enclosed in?
- some are enclosed within an envelope, derived from host cell membranes and modified by inclusion of viral glycoproteins
380
what is a capsid?
- surrounding coat of protein that can enclose a virion
| - composed of capsomeres (distinct morphological units) which are assembled from viral proteins
381
what are capsomeres?
- morphological units that make up the capsid
- assembled from viral proteins
- depending on the arrangement of the
382
why are viruses important?
viruses are a common and significant cause of human disease globally, and nationally in the UK
383
what is a virus?
an infectious, obligate intracellular parasite comprising genetic material (DNA or RNA) surrounded by a protein coat and/or membrane
- receptor binding protein to dock to cells
- all contain genetic material
384
what is an obligate intracellular organism?
- totally dependent on living cells for their replication and existance
385
what are shapes of viruses?
helical, icosahedral, complex
386
what do virions consist of?
- genetic material (DNA or RNA)
| - protein coat (capsid)
387
what do viruses exist as when not inside an infected cell?
virions
388
what is the envelope of a virus?
- can be enveloped or non-enveloped
| - lipid coat derived from plasma membrane of the host cell
389
what shapes can the nucleocaspid be?
nuclecaspid is the protein coat of a virus and the genetic material
- helical (spiral staircase e.g. influenza)
- icosahedral (cubic e.g. adenovirus) in symmetry
390
what are examples of different sizes of viruses?
from large to small:
- poxvirus
- rhabdovirus
- herpesvirus
- adenovirus
- parvovirus
20-260 nm in diameter
391
what are the basic properties of viruses vs bacteria?
viruses
- no cell wall
- no organelles
- no DNA and RNA (both)
- is dependent on host cell
- not living (do not feed or respire, can't reproduce independently)
bacteria
- cell wall
- organelles
- DNA and RNA
- not dependent on host cell
- is living
392
why are viruses not living?
- do not feed
- do not respire
- can't reproduce independently
393
how do viruses replicate?
1. attachment to specific receptor (dictates the type of cells that viruses can infect)
2. cell entry (uncoating of virion within cell)
3. host cell interaction and replication
4. assembly of virion
5. release of new virus particles
394
what parts of the virus enter the cell?
only central viral core carrying the nucleic acid and some associated proteins
395
what happens in host cell interaction and replication of viruses?
- migration of genome to cell nucleus
- transcription to mRNA using host materials
- uses cell materials (enzymes, amino acids, nucleotides) for replication; subvert host cell defence mechanisms
- translation of viral mRNA to produce structural proteins, viral genome and non-structural proteins
396
where does assembly of the virion occur?
different locations depending on virus
- nucleus (e.g. herpes viruses)
- cytoplasm (e.g. poliovirus)
- at cell membrane (e.g. influenza virus)
397
what happens in the release of new virus particles?
a: bursts out -> cell death e.g. rhinovirus
b: budding/exocytosis e.g. HIV, influenza
398
how do viruses cause disease?
- direct destruction of host cells
- modification of host cell
- over reactivity of immune system
- damage through cell proliferation
- evasion of host defences
399
what is an example of direct destruction of host cells by viruses?
- poliovirus -> host cell lysis and death after a viral replication period of 4 hours
- lysis of neurons -> paralysis
400
what is an example of modification of host cell by viruses?
rotavirus
- atrophies villi and flattens epithelial cells
- decreases small intestine SA
- nutrients including sugar are not absorbed
- hyperosmotic state
- profuse diarrhoea
rotavirus is resistant to acidic pH
401
what is an example of over reactivity of the immune system to viruses?
hepatitis B
- viral antigen binds to hepatocyte by MHC class 1
- cytotoxic T lymphocyte
- > jaundice, pale stool, dark urine, RUQ pain, fever + malaise, itching
402
what is an example of damage through cell proliferation by viruses?
human papillomavirus -> cervical cancer
- acquisition through contact
- partial viral replication and expression of some HPV proteins
- viral DNA integrated into host chromosome
- continuous expression of oncoproteins causing cellular DNA mutations
- dysplasia and neoplasia -> cell proliferation and local/metastatic spread
403
what cancers is HPV associated with?
cervical, penile, anal, vaginal, vulval and head/neck cancer
404
what are the steps involved in HPV infection causing cervical cell carcinoma?
1. HPV (types 16 or 18) infection of suprabasal layer in genital tract
2. partial viral replication including transcription and expression of several early viral gene products (E1, E2, E4, E5)
3. gradual movement of cells to mucosal surface through natural wear and tear
4. at some point, HPV genome may integrate into the host cell chromosome. mutagenic agents (e.g. nicotine) may increase the chance of integration
5. following integration, control of viral gene expression by the HPV E2 protein is lost and HPV E6 and E7 may be expressed
6. Rb and p53 are prevented from operating
7. excessive cell growth and proliferation occurs and cervical cell carcinoma results
405
what viruses affect the nerve root cell ganglion?
HSV 1+2
| VSV
406
what viruses affect lymphoid cells?
EBV
| HHV-8
407
what viruses affect myeloid cells?
HHV-6
HHV-7
CMV
408
what is VZV?
Varicella Zoster Virus
409
what is the primary infection and reactivation of VZV?
- chickenpox
| - shingles/herpes zoster
410
what are the cellular levels at which viruses can evade host defences? give examples
- latency e.g. herpesviridae
| - cell-cell spread e.g. measles, HIV
411
what are the advantages of direct cell to cell spread of viruses?
- avoids random release into the environment
- increased speed of spread within tissues
- avoiding immune system
412
how do viruses use antigenic variability to evade host defences? what does this explain? give examples
ability to change the surface antigens in order to evade host's immune system
- e.g. influenza, HIV, rhinovirus
- explains how a host can be reinfected with the same virus e.g. common cold and why the influenza vaccination is required annually, as each season a different viral strain is circulating
413
how does preventing apoptosis of cells by viruses help them evade host defences? give an example
- allows virus to continue replicating within it, so more virus is produced and then released
- has a role in how some viruses are oncogenic
- normally, viral infected cells undergo apoptosis so the amount of virus released is reduced
- e.g. herpesviridae
414
how does downregulation of interferon and other intracellular host defence proteins by viruses allow them to evade host defences?
- stimulated interferon synthesis leads to an activated antiviral state in neighbouring cells
- blocking interferon synthesis leads to neighbouring cells being susceptible to infection
415
what are the molecular level mechanisms that viruses use to evade host defences?
- antigenic variability e.g. influenza, HIV, rhinovirus
- prevention of host cell apoptosis, e.g. herpes viridae, HIV
- downregulation of interferon and other intracellular host defence proteins
- interference with host cell antigen processing pathways e.g. herpesviridae, measles, HIV
416
what are some key points about viruses?
- viruses are a common and significant cause of human disease globally, and nationally in the UK
- viruses are very small, consist of genetic material surrounded by a capssid (protein coat) - not living
- a virus is completely dependent on its host cells machinery to exist and replicate and enters a cell with only its genome and/or viral enzymes
- viruses vary wildly in range of clinical syndromes
417
why do viruses vary wildly in the range of clinical syndromes they can cause?
- different host cells and tissues that they can infect
| - different methods of interaction with the host cell
418
what conditions can herpes simplex virus cause?
skin
- orofacial herpes
- genital herpes
- herpetic whitlow
- erythema multiforme
- herpes gladiatorum
visceral
- oesophagitis
- pneumonitis
- hepatitis
CNS
- meningitis
- encephalitis
- transverse myelitis
eye
- conjunctivitis
- keratitis
419
what can JC virus cause?
CNS
| - progressive multifocal leukoencephalopathy
420
what viruses can cause encephalitis/meningitis?
- JC virus
- measles
- LCM virus
- arbovirus
- rabies
421
what viruses can cause common cold?
- rhinovirus
- parainfluenza virus
- respiratory syncytial virus
422
what viruses can cause pharyngitis?
- adenovirus
- epstein-barr virus
- cytomegalovirus
423
what viruses can cause gingivostomatitis?
- herpes simplex type 1
424
what viruses can cause cardiovascular problems?
- coxsackie B virus
425
what viruses can cause hepatitis?
- hepatitis virus types A, B, C, D, E
426
what viruses can cause skin infections?
- VZV
- human herpesvirus 6
- smallpox
- molluscum contagiosum
- human papillomavirus
- parvovirus B19
- rubella
- measles
- coxsackie A virus
427
what viruses can cause STDs?
- herpes simplex type 2
- human papillomavirus
- HIV
428
what virus can cause pancreatitis?
- coxsackie B virus
429
what viruses can cause gastroenteritis?
- adenovirus
- rotavirus
- norovirus
- astrovirus
- coronavirus
430
what viruses can cause myelitis?
- poliovirus
| - HTLV-I
431
what viruses can cause pneumonia?
- influenza virus types A and B
- parainfluenza virus
- respiratory syncytial virus
- adenovirus
- SARS coronavirus
432
what viruses can cause parotitis?
- mumps virus
433
what viruses can cause eye infections?
- herpes simplex virus
- adenovirus
- cytomegalovirus
434
what are the methods of diagnosing viral infections?
- PCR (is viral genetic material present?)
- serology (is there immune memory to a virus?)
- histopathology (are there any features of viral infection present?
- viral culture and light microscopy
- electron microscopy
435
what are the four species of malaria parasites that are commonly encountered in human disease? what do they cause?
Plasmodium falciparum: causes most fatalities
P. vivax and P. ovale: cause benign tertian malaria
P. malariae: causes quartan malaria
P. knowlesi (parasite of long-tailed macaque monkeys) may also affect humans
436
what is the life cycle of malaria parasites?
1. when an infected mosquito bites (blood meal), sporozites present in the salivary glands enter the bloodstream and are carried to the liver
2. sporozites invade the liver parenchymal cells
3. multiple nuclear division to form a schizont
4. schizogony of the shizont (cytoplasmic division)
5. liver cell ruptures releasing thousands of individual parasites (merozoites) into the bloodstream
6. merozoites penetrate erythrocytes and adopt a signet-ring morphology
7. in bloodstream, trophozites (young ring forms) and undergo nuclear division (erythrocytic schizogony) to form shizont, which rupture and release merozoites
8. 8-24 nuclei are produced, and erythrocyte ruptures to release merozoites which infect fresh erythrocytes
437
what is a merozoite?
- individual parasites (of malaria)
438
what is schizogony?
asexual division of sporozoa
439
what is sporogony?
sexual development of sporozoa
440
what are hypnozoites?
parasites that remain dormant
- e.g. P. virax and P. ovale remain dormant in the liver and the cycle of pre-erythrocytic schizogony is completed after a long delay
- responsible for relapses of tertian malaria that may occur
- relapses weeks to years later
441
what are trophozoites?
young ring forms of malarial parasites
442
what is the process that some merozoites go through if they don't enter the cycle of erythrocytic schizogony?
- develop within red cells into male or female gametocytes
- don't develop further in the human host
- when the insect vector ingests the blood, the nuclear material and cytoplasm of male gametocytes differentiate to produce several individual gametes (extraflagellating male gametocyte)
- gametes detach and penetrate the female gametocyte, which elongates into the zygotic form, the ookinete
- ookinete penetrates the mid-gut wall of the mosquite and settles as an oocyst, within which many sporozoites are formed
- when mature, the oocyst rupture and releases them into the body cavity, some go to the salivary glands
- mosquito ingests gametocytes
- ingested gametocytes are reinjected into next person
443
what is an extraflagellating male gametocyte?
- malarial parasites
- nuclear material and cytoplasm of male gametocytes in erythrocytes differentiate to produce several individual gametes, giving the appearance of a flagellate body
444
what is an ookinete (protozoa)?
- forms when extraflagellating male gametocytes become detached and penetrate the female gametocyte, which elongates into this zygotic form (ookinete)
445
how does P. falciparum differ from other forms of malaria parasite in its mechanism of action?
- developing erythrocytic schizonts form aggregates in the capillaries of the brain and other internal organs
- normally only relatively young ring forms or gametocytes (crescent shaped) are found in peripheral blood
446
what are differential characteristics of P. falciparum in Romanowsky-stained thin films of peripheral blood?
- ring forms only (trophozoite morphology)
- normal morphology of red cell
- Maurer's spots (stippling of red cell)
- crescentic morphology of gametocyte
- 16-24 merozoites in mature schizont
447
what are differential characteristics of P. vivax in Romanowsky-stained thin films of peripheral blood?
- rings, becoming amoeboid during development (trophozoite morphology)
- enlarged morphology of red cell
- Schueffner's dots (stippling of red cells)
- large, round morphology of gametocyte
- 16-24 merozoites in mature schizont
448
what are differential characteristics of P. ovale in Romanowsky-stained thin films of peripheral blood?
- rings, becoming compact during development (trophozoite morphology)
- slightly enlarged, somtimes oval with fimbriate edge morphology of red cell
- James's stippling of red cell
- round morphology of gametocyte
- 8-12 merozoites in mature schizont
449
what are differential characteristics of P. malariae in Romanowsky-stained thin films of peripheral blood?
- rings, becoming compact/stretched across red cell (trophozoite morphology)
- normal or slightly shrunken morphology of red cell
- Ziemann's dots (stippling of red cell)
- small, round morphology of gametocyte
- 8-12 merozoites in mature schizont
450
how long does the cycle of erythrocytic schizogony take?
48 hours
| - except in P. malariae, where it is 72 hrs
451
what is the laboratory diagnosis of acute falciparum malaria?
- medical emergency that demands immediate diagnosis and treatment
- drop of peripheral blood is spread on a glass slide
- smear should not be too thick
- dries thoroughly and is stained by Field's method (acute Romanowsky stain)
- water used to dilute the stain should be pH 7.2
452
what are other diagnostic tests for the rapid diagnosis of malaria?
dipstick tests
| - tests that detect P. falciparum alone or distinguish between P. falciparum and P. virax are available
453
what is the pathogenesis of malaria?
- severe chills, high fever and sweating, headache, muscle pains and vomiting
- falciparum malaria may progress to coma, convulsions and death
454
how does falciparum malaria affect people?
- may progress to coma, convulsions and death
- cerebral malaria is associated with adherence of parasitised red blood cells to the endothelium of brain capillaries
- severe anaemia and renal failure, hypoglycaemia, pulmonary oedema and gastroenteritis
455
what are protective factors against malaria?
- individuals homozygous or heterozygous for the sickle cell gene have much-reduced susceptibility to infection with P. falciparum
- individuals whose red cells lack the antigen known as the Duffy factor are protected against P. vivax
456
what is the treatment of malaria?
- P. falciparum is resistant to chloroquine
- derivatives of artemisinin (natural product from the plant Artemisia annua) including artemether and sodium artesunate are quick acting and effective
- quinine
- antibiotics, e.g. tetracyclines and clindamycin
- mefloquine and halofantrine are active against chloroquine resistant strains, but there is increased resistance and toxicity
- 8-aminoquinoline drug primaquine; used for eliminating parasites from the liver
457
what are recommendations for antimalarial prophylaxis?
- combination of atovaquone and proguanil daily
- combination of daily proguanil and weekly chloroquine
- mefloquine, once a week
- daily doxycycline or primaquine
458
how long should antimalarial prophylaxis go on for?
- at least 4 weeks
- because parasites in pre-erythrocytic stage of development escape action of most prophylactic drugs
- prevents development of falciparum malaria
- relapses can occur up to 2 years after exposure
459
what is Toxoplasma gondii?
- coccidian parasite of the intestinal tract of the cat
- transmissible to many other mammals
- occurs worldwide
- transient febrile illness or subclinical attack
- transmission: ingestion of undercooked meat/shellfish, contact with feline faeces, vertical transmission
460
what are examples of severe infection with Toxoplasma gondii?
- intra-uterine toxoplasmosis is an important cause of stillbirth and congenital abnormality
- ocular disease is rare but serious
- cerebral toxoplasmosis sometimes occurs in immunocompromised patients
- severe consequences in pregnancy and immunodeficiency
- disseminated disease, toxoplasma encephalitis, retinochoroiditis
461
what is the mechanism of Toxoplasma gondii infection?
- mature oocysts excreted by infected cats contain 2 sporocysts
- tachyzoites develop within them
- on ingestion, the tachyzoites pass to the bloodstream and lymphatics to invade macrophages, and multiply
- as the immune system develops, other cells are infected and tissue cysts containing slowly metabolising bradyzoites are formed
462
how is Toxoplasma gondii infection acquired?
- ingestion of oocysts or of tissue cysts in undercooked meat
- intra-uterine infection is acquired transplacentally
463
how is Toxoplasma gondii infection diagnosed?
- demonstration of rising titre of serum antibodies to Tox. gondii
- Sabin-Feldman dye exclusion test recognises the ability of serum antibody to kill viable toxoplasmas
- ELISA avoids use of live toxoplasmas
- PCR for intra-uterine and cerebral infections
464
what is the treatment of Toxoplasma gondii infection?
- combination of pyrimethamine and a sulphonamide is effective against active tachyzoitese
- spiramycin is effective and may be preferred in pregnancy
- clindamycin, azirthromycin and atovaquone, in combination with pyrimethamine, are alternatives for patients with cerebral toxoplasmosis
465
what is Isospora belli?
- coccidian parasite
| - common in areas with poor sanitation
466
what are the signs, diagnosis and treatments for Isospora belli infection?
- self-limiting diarrhoea, sometimes more severe, esp. in AIDS
- oocysts can be seen in faecal wet mounts; poorly refractile and easily missed
- co-trimoxazole is effective
467
what is Cryptosporidium parvum infection?
- cryptosporidia are common animal parasites
- causes watery diarrhoea in humans, vomiting, fever, fatigue, especially infants
- infection is usually waterborne or acquired from animals or infected cases
- self limiting 2-3 weeks
468
what is the diagnosis and treatment of Cryptosporidium parvum infection?
- large numbers of oocysts are present in faeces; they are partially acid-fast and can be demonstrated by modifications of the ZN methods
- responds to symptomatic treatment with fluid replacement if needed
- in severely immunocompromised patients, it may cause severe life-threatening diarrhoea for which nitazoxanide or macrolides e.g. azithromycin may be beneficial
469
what is Cyclospora cayetanensis?
- unlike cryptosporidia, cyclospora develop intracellularly in the gut mucosa
- associated with poor sanitation
- causes diarrhoea
470
what is the diagnosis and treatment of Cyclospora cayetanensis?
- immature oocysts are excreted in the faeces as round bodies about 10um in diameter
- mulberry appearance
- more variably acid-fast than cryptosporidia
- infection is more severe in the immunocompromised
- mild infection is treated symptomatically, with rehydration if needed
- co-trimoxazole is effective in serious infection
471
what is Sarcocystis species?
- animal parasites Sarcocystis bovihominis and S. suihominis may invade the human intestinal tract or muscle
- infection is usually subclinical and discovered accidentally
472
what is Entamoeba histolytica? what are the effects?
- most important amoebic parasite in man
- invades the colonic mucosa, producing ulcerative lesions and profuse bloody diarrhoea
- systemic infection may arise, leading to abscess formation in internal organs, e.g. the liver
- may arise in absence of frank dysentery
473
what is the laboratory diagnosis of Entamoeba histolytica?
- in acute amoebiasis, blood stained mucus or colonic scrapings from ulcerated areas are examined by direct microscopy
- material should be examined within 2hours of collection
- active movement, pushing out fingerlike pseudopodia and progressing across microscope field
- if mucosal invasion has occurred, amoebae contain ingested red cells (absent if infection is confined to the gut lumen)
- nucleus is a delicate ring of chromatin with a central karyosome in fixed spears stained with haemotoxylin
474
what are the structures of amoeba?
- encysted form is how infection is spread
- spherical, 10-15um in diameter
- nuclei
- young uninucleate cysts may contain a large glycogen vacuole
- in fresh specimens, there may be one or more thick, blunt-ended chromatoidal bars
- red cells
- flagellum
- cytosome
- sucking pads with nuclei
475
what is the treatment of entamoeba histolytica?
- metronidazole and tinidazole have superseded older drugs e.g. emetine and dehydroemetine for treatment of amoebic dysentery and amoebic liver abscess
- diloxanide furoate is used
476
what are the differential characteristics of Entamoeba histolytica?
trophozoites
- 10-40um
- ingested red blood cells present
cysts
- 10-15 um
- 4 nuclei
- solid, blunt ended chromatoidal bars
- free ring of chromatin with central karyosome
477
what are the differential characteristics of E. hartmanni?
trophozoites
- 4-10um
- no ingested red blood cells
cysts
- 6-10um
- 4 nuclei
- solid, blunt ended chromatoidal bars
- fine ring of chromatin with central karyosome
478
what are the differential characteristics of E. coli?
trophozoites
- 10-40um
- no ingested red blood cells
cysts
- 15-25um
- 8 nuclei
- slender, ponted chromatoidal bars
- fine ring of chromatin with eccentric karyosome
479
what are the differential characteristics of E. gingivalis?
trophozoites
- 10-25um
- no ingested red blood cells
no cyst stage
480
what are the differential characteristics of Iodamoeba butschlii?
trophozoites
- 10-20um
- no ingested red blood cells
cysts
- 10-15um
- 1 nuclei
- no chomatoidal bars
- chromatin massed at one end of ring
481
what are the differential characteristics of Endolimax nana?
trophozoites
- 5-12um
- no ingested red blood cells
cysts
- 5-8um
- 4 nuclei
- no chromatoidal bars
- small shadowy masses of chromatin
482
what are differential characteristics of Dientamoeba fragilis?
trophozoites
- 5-10um
- no ingested red blood cells
no cyst stage
ring containing several chromatin granules
483
what are some examples of free living amoebae? what can they cause?
- environmental amoebae belonging to the genus Naegleria are implicated in meningo-encephalitis
- rare cases of granulomatous encephalitis caused by Balamuthia mandrillaris and Acanthamoeba have been described in immunocompromised patients
- Acanthamoeba spp. cause keratitis commonly
484
what is Giardia lambilia? what can this lead to?
- flagellate
- intestinal parasite living attached to the mucosal surface of the upper small intestine
- may lead to absorption of fat and chronic diarrhoea
- infection is usually water borne
- diarrhoea, cramping, bloating
- foecal oral spread
diagnosis: stool microscopy (cysts and trophozoites)
485
what is the structure/location of Giardia lambilia trophozoites?
- trophozoite is kite shaped, with two nucleated sucking pads and four pairs of flagella
- trophozoites may be found in duodenal aspirate
486
what is the structure of Giardia lambilia cysts?
- oval, 10 x 8um, contains up to 4 nuclei and the remains of the skeletal structure of the trophozoite
487
what is the treatment of Giardia lambilia?
5-nitroimidazoles such as matronidazole or when this fails, with albendazole or mepacrine
- tinazole, metranidazole
488
what is Trichomonas vaginalis? what is its structure? what is it transmitted by?
- flagellate protozoon with four anterior flagella and one lateral flagellum attached to the surface of the parasite to form an undulating membrane
- no cyst form
- transmitted by sexual intercourse
- motile
489
what does T. vaginalis lead to? what is its treatment?
- mild vaginitis with discharge
| - treated by metronidazole or tinidazole
490
what is African trypanosomiasis?
- african sleeping sickness is caused by trypanosomes that are subspecies of Trypanosoma brucei
- tsetse flies act as the insect vector
- human parasites are T. brucei gambiense, which occurs in riverine areas of west and central Africa and T. brucei rhodesiense, a parasite of the savannah plains of east africa
491
what is the pathogenesis of Trichomonas vaginalis?
- after the bite of an infected tsetse fly, a localised trypanosomal chancre may appear transiently, but invasion of the bloodstream rapidly occurs
- parasites multiply in blood
- swollen lymph glands in the posterior triangle of the nect are present in T. brucei gambiense infection
- if untreated, the disease progresses to involve the CNS with classical signs of sleeping sickness, then death
492
how is trypanosomes diagnosed?
- can be found in peripheral blood in unstained wet mounts or in smears stained by Giemsa or Leishman methods
- examination of CSF reveals a lymphocytic exudate, with morula cells and sparse motile trypanosomes
- parasites are elongated, 20-30um in length, with a single anterior flagellum arising via an undulating membrane from a basal body situated near a posteriorly placed kinetoplast
493
what are forms that may be adopted by Leishmania and Trypanosomia spp.?
- amastigote (leishmanial form or Leishman-Donovan body)
- promastigote (leptomonad form)
- epimastigote (crithidial form)
- trypomastigote (trypanosome form)
494
what is the structure of the amastigote?
- kinetoplast
| - nucleus
495
what is the structure of the promastigote?
- flagellum
- kinetoplast
- nucleus
496
what is the structure of the epimastigote?
- flagellum
- undulating membrane
- kinetoplast
- nucleus
497
what is the structure of the trypomastigote?
- flagellum
- undulating membrane
- nucleus
- kinetoplast
498
what is the treatment of trypanosomes?
- suramin or pentamidine for the early parasitaemic stage
- trivalent arsenicals, melarsoprol or tryparsamide for when the disease progresses to sleeping sickness
- less toxic alternatives are required; eflornithine is effective in T. brucei gambiense infections, but not in disease caused by T. brucei rhodesiense
499
what is Chagas' disease caused by?
T. cruzi
| - insect vectors are various species of reduviid bugs
500
what is the action of T. cruzi in causing Chagas' disease?
- trypanosomes are present in bug faeces
- unwitting sleeper rubs into bite wound
- do not multiply in the bloodstream
- invade cells of the reticuloendothelial system and muscle, where they lose their flagellum and undulated membrane and adopt a rounded shape
- morphological form is an amastigote
- amastigotes multiple in muscle and are liberated from ruptured cells as trypansomal forms which disseminate the infection
501
what is the pathogenesis of Chagas' disease?
- chronic condition
- extensive cardiomyopathy
- gross distension of other organs
- death is usually from heart failure
502
what are laboratory diagnoses of Chagas' disease?
- PCR and immunoassays are used for serological diagnosis
- direct microscopy of peripheral blood
- culture in rich blood agar medium
- mouse inoculation
- xenodiagnosis: uninfected reduviid bugs are allowed to feed on the patient and after 3-4 weeks the gut contents of the bug are examined for trypanosomes
503
what is the treatment of Chagas' disease?
- no reliable chemotherapy
| - nitrofuran derivative nifurtimox and imidazole compound benznidazole have been used
504
what are Leishmania species? what forms do they exist in? how are they transmitted?
- intracellular parasites of the reticuloendothelial system
- related to trypanosomes
- exist in amastigotes (non-flagellate forms) and promastigotes (flagellate forms that lack an undulating membrane)
- vector: female sandflies
- middle east, india, south america, mediterranean littoral, parts of africa (poverty
505
what Leishmania species are involved in human disease, and what form of disease are they?
```
Leishmania tropica (cutaneous)
L. major (cutaneous)
L. aethiopica (cutaneous, DCL)
L. donovani (visceral)
L. infantum (visceral)
L. chagasi (visceral)
L. mexicana complex (cutaneous, DCL)
L. brazillienis complex (mucocutaneous)
L. peruviana (cutaneous)
```
506
what is treatment of Leishmania disease?
- penvalent antimony compounds, sodium stibogluconate and meglumine antimoniate, have been used, but are toxic and often fail
- amphotericin B is effective but poorly tolerated
- antifungal azoles and paromomycin have been used in cutaneous disease
- miltefosine used in kala azar
507
what are babesia species?
- predominantly animal species
- intracellular parasites living within red blood cells
- transmitted by ixodid ticks
- Babesia divergins and B. microti have caused disease
- combination of quinine with clindamycin has been used
508
what is leprosy? what is it caused by?
- Hansen's disease
- tuberculosis
- respiratory disease
- chronic granulomatous disease affecting skin and nerves
- caused by Mycobacterium leprae: slow growing mycobacterium that cannot be cultured in vitro
509
what are the clinical manifestations of leprosy determined by?
- by the degree of the patient's cell mediated immunity (CMI) towards M. leprae
- high levels of CMI with elimination of leprosy bacilli produces tuberculoid leprosy
- absent CMI produces lepromatous leprosy
510
what are the complications of leprosy due to?
- due to nerve damage, immunological reactions and bacillary infiltration
511
what is the epidemiology and transmission of leprosy?
- 4 million people have leprosy
- 750000 new cases are detected annually
- 70% of the world's leprosy patients live in India, with endemics in Brazil, Indonesia, Mozambique, Madagascar, Tanzania and Nepal
- untreated lepromatous patients discharge bacilli from the nose; infection occurs through the nose, followed by haematogenous spread to skin and nerve
- incubation period is 2-5 years for tuberculoid cases and 8-12 years for lepromatous cases
- incidence peaks at 10-14 years
- more common in males and in those with close household exposure to leprosy cases
512
what is the pathogenesis of leprosy?
- M. leprae has a predilection for infecting Schwann cells and skin macrophages
- in tuberculoid leprosy, effective CMI controls bacillary multiplication (paucibacillary), organised epithelioid granulomas are formed
- in lepromatous leprosy, there is abundant bacillary multiplication (multibacillary) e.g. in Schwann cells and the perineurium
- moderate CMI (borderline tuberculoid) to patients with little cellular response (borderline lepromatous)
513
what is paucibacillary and multibacillary leprosy?
paucibacillary: effective CMI control of bacillary multiplication in tuberculoid leprosy
multibacillary: abundant bacillary multiplication in Schwann cells and the perineurium
514
what is borderline tuberculoid and borderline lepromatous leprosy?
borderline tuberculoid: moderate CMI
borderline lepromatous: patients with little cellular response
515
what are immunological reactions to leprosy?
- occur as the immune response develops and the antigenic stimulus from the bacilli varies, particularly in borderline patients
- delayed hypersensitivity reactions produce type 1 (reversal) reactions
- immune complexes contribute to type 2 (erythema nodosum leprosum) reactions
516
what is the appearance in HIV/leprosy co-infected patients?
- typical lepromatous and tuberculoid skin lesions and typical leprosy histology and granuloma formation
- even with low circulating CD4 counts, tuberculoid leprosy may be observed and there is not an obvious shift to lepromatous leprosy
517
what are clinical features of leprosy in the skin?
- most common skin lesions are macules or plaques
- hypopigmented lesions
- in lepromatous leprosy, papules, nodules or diffuse infiltration of the skin occur
- earliest lesions are ill defined
- gradually, skin becomes infiltrated and thickened
- facial skin thickening leads to the characteristic leonine facies
518
what are clinical features of leprosy in anaesthesia?
- in skin lesions, the small dermal sensory and autonomic nerve fibres are damaged, causing local sensory loss and loss of sweating within that area
- anaesthesia may occur in the distribution of a damaged large peripheral nerve
- glove and stocking sensory neuropathy is common in lepromatous leprosy
519
what are clinical features of leprosy in nerve damage?
- peripheral nerve trunks are damaged at sites of predilection: ulnar, median, radial, radial cutaneous, common peroneal, posterior tibial and sural nerves, facial nerve, great auricular nerve
- damage to peripheral nerve trunks produces characteristic signs with regional sensory loss and muscle dysfunction
- all nerves should be examined for enlargement and tenderness and tested for motor and sensory function
- CNS not affected
520
what are the sites of predilection for peripheral nerve trunks?
- ulnar (elbow)
- median (wrist)
- radial (humerus)
- radial cutaneous (wrist)
- common peroneal (knee)
- posterior tibial and surfal nerves (ankle)
- facial nerve (zygomatic arch)
- great auricular nerve (posterior triangle of the neck(
521
what are clinical features of leprosy in eye involvement?
- blindness
- eyelid closure is impaired when the facial nerve is affected
- damage to the trigeminal nerve causes anaesthesia of the cornea and conjunctiva
- cornea susceptible to trauma and ulceration
522
what are micellaneous clinical features of leprosy?
- many organs can be affected
- nasal collapse occurs secondary to bacillary destruction of the bony nasal spine
- diffuse infiltration of the testes causes testicular atrophy and the acute orchitis that occurs with type 2 reactions
- results in azoospermia and hypogonadism
523
what are the cardinal features of leprosy?
- skin lesions, typically anaesthetic at tuberculoid end of spectrum
- thickened peripheral nerves
- acid-fast bacilli on skin smears or biopsy
524
what are skin and nerve features like in lepromatous vs tuberculoid leprosy?
number and distribution
- L: widely disseminated
- T: one or a few sites, asymmetrical
525
what are skin lesions like in lepromatous vs tuberculoid leprosy?
```
clarity of margin
L: poor
T: good
elevation of margin
L: never
T: common
```
```
dark skin
L: slight hypopigmentation
T: marked hypopigmentation
light skin
L: slight erythema
T: coppery or red
```
surface
L: smooth; shiny
T: dry; scaly
central heating
L: none
T: common
sweat and hair growth
L: impaired late
T: impaired early
loss of sensation
L: late
T: early and marked
526
what is nerve enlargement and damage like in lepromatous vs tuberculoid leprosy?
L: late
T: early and marked
527
what is bacilli like in lepromatous vs tuberculoid leprosy?
L: many (5 or 6+)
T: absent
528
what is the natural history of lepromatous vs tuberculoid leprosy?
L: progressive
T: self healing
529
what are the reactions like in lepromatous vs tuberculoid leprosy?
L: immune complexes (type 2)
T: cell mediated (type 1)
530
what are leprosy reactions?
events superimposed on the cardinal features
531
what are type 1 (reversal) reactions in leprosy? what happens in them? when do they occur?
- occur in 30% of borderline patients (BT, BB or BL) and are delayed hypersensitivity reactions
- skin lesions become erythematous
- peripheral nerves become tender and painful, with sudden loss of nerve function
- reactions may occur spontaneously, after starting treatment and after completing multidrug therapy
532
what are type 2 leprosy reactions? what happens in them? when do they occur?
- erythema nodosum leprosum (ENL)
- partly due to immune complex deposition
- occur in BL and LL patients who produce antibodies and have a high antigen load
- manifest with malaise, fever and crops of small pink nodules on the face and limbs; iritis and episcleritis are common
- other signs are acute neuritis, lymphadenitis, orchitis, bone pain, dactylitis, arthritis and proteinuria
- may continue intermittently for several years
533
what are the features of borderline tuberculoid (BT) cases?
- skin lesions are more numerous than in tuberculoid cases, and there is more severe nerve damage and risk of type 1 infections)
534
what are features of borderline leprosy (BB) cases?
- numerous skin lesions that vary in size, shape and distribution
- annular lesions are characteristic
- nerve damage is variable
535
what are features of borderline lepromatous (BL) cases?
- widespread small macules in the skin
- widespread nerve involvement
- both type 1 and 2 reactions occur
536
what is pure neural leprosy? what are its features?
- leprosy without skin lesions
- occurs principally in India and accounts for 10% of patients
- asymmetrical involvement of peripheral nerve trunks and no visible skin lesions
- on nerve biopsy, all types of leprosy have been found
537
what is the investigation of leprosy?
- diagnosis is critical; made by finding a cardinal sign of leprosy and supported by finding acid-fast bacilli in slit-skin smears or typical histology in a skin biopsy
- slit-skin smears obtained by scraping dermal material on to a glass slide
- smears are stained for acid-fast bacilli, the number counted per high power field and a score derived on a logarithmic scale (0-6): the bacterial index
- serology nor PCR testing for M. leprae DNA is sensitive/specific enough for diagnosis
538
how are slit-skin smears obtained? what is done to the smears?
- obtained by scraping dermal material onto a glass slide
- smears are stained for acid fast bacilli
- the bacterial index is calculated
- useful for confirming the diagnosis and monitoring response to treatment
539
how is the bacterial index calculated?
- slit-skin smears are stained for acid-fast bacilli
| - number of acid-fast bacilli is counted per high-power field and a score derived on a logarithmic scale (0-6)
540
what are the principles of leprosy treatment?
- stop the infection with chemotherapy
- treat reactions
- educate the patient about leprosy
- prevent disability
- support the patient socially and psychologically
541
what is the mechanism of Lepra reaction type 1 (reversal)?
cell mediated hypersensitivity
542
what is the mechanism of Lepra reaction type 2 (erythema nodosum leprosum)?
immune complexes
543
what are the clinical features of type 1 leprosy reaction (reversal)?
- painful tender nerves, loss of function
- swollen skin lesions
- new skin lesions
544
what are the clinical features of type 2 leprosy reaction (erythema nodosum leprosum)?
- tender papules and nodules; may ulcerate
- painful tender nerves, loss of function
- iritis, orchitis, myositis, lymphadenitis
- fever, oedema
545
what is the management of type 1 leprosy reactions?
Prednisolone 40mg, reducing over 3-6 months
546
what is the management of type 2 leprosy reactions?
moderate: Prednisolone 40mg daily
severe: thalidomide or prednisolone 40-80mg daily, reducing over 1-6 months; local if eye involved
547
what are the types of treatments and duration given for paucibacillary leprosy?
monthly supervised treatment: Rifampicin 600mg
daily self administered treatment: Dapsone 100mg
duration of treatment: 6 months
548
what are the types of treatments and duration given for multibacillary leprosy?
monthly supervised treatment: Rifampicin 600mg and Clofazimine 300mg
daily self administered treatment: Clofazimine 50mg and Dapsone 100mg
duration of treatment: 12 months
549
what are the types of treatments and duration given for paucibacillary single-lesion leprosy?
monthly supervised treatment: Ofloxazin 400mg, Rifampicin 600mg and Minocycline 100mg
duration of treatment: single dose
550
what are the characteristics of leprosy treatments/medications?
- rifampicin is a potent bactericidal for M. leprae but should be given in combination with other anti-leprotics, as a sing;e-step mutation can cofer resistance
- dapsone is bacteriostatic; commonly causes mild haemolysis and rarely anaemia
- clofazimine is a red, fat soluble crystalline dy, weakly bactericidal for M. leprae. can cause skin discolouration and ichthyosis
- new and second-line drugs: fluoroquinolones pefloxacin and ofloxacin, minocycline and clarithromycin
551
what is the prognosis of leprosy?
- untreated tuberculoid leprosy has a good prognosis; it may self heal and peripheral nerve damage is limited
- lepromatous leprosy is a progressive condition with high morbidity if untreated
- after treatment, most patients, especially ones with no nerve damage at diagnosis, do well with resolution of skin lesions
- borderline patients are at risk of developing type 1 reactions, which may result in devastating nerve damage
552
what is the prevention and control of leprosy?
- previous strategy of centralised leprosy control campaigns has been superseded by integrated programmes
- primary health-care workers are often responsible for case detection and provision of MDT
- BCG gives good but variable protection against leprosy; adding killed M. leprae doesn't enhance protection
553
what is the epidemiology of tuberculosis (TB)?
- caused by infection with Mycobacterium tuberculosis (MTB), part of a complex of organisms including M. bovis (reservoir cattle) and M. africanum (resevoir human)
- decline in incidence of TB
- in 2010, there were 8.8 million cases and it caused 1.5 million deaths
- 1/3 of the world population has latent TB
- majority of cases occur in the world's poorest nations, who struggle to cover costs for management and control programmes
554
what is TB caused by?
by infection with Mycobacterium tuberculosis (MTB), which is part of a complex of organisms including M. bovis (resevoir cattle) and M. africanum (resevoir human)
555
what is the pathology and pathogenesis of TB? how does MTB spread?
- M. bovis infection arises from drinking non-sterilised milk from infected cows
- M. tuberculosis is spread by inhalation of aerosolised droplet nuclei from other infected patients
- organisms lodge in the alveoli and initiate recruitment of macrophages and lymphocytes
- macrophages undergo transformation into epitheliod and Langhans cells, which aggregate with lymphocytes to form tuberculous granuloma
- primary lesion is formed in the periphery of the lung
- primary complex of Ranke forms
556
why has there been a resurgence of TB in Africa and in the Soviet Union and Baltic states?
Africa: HIV disease
| SU and Baltic states: lack of appropriate health care associated with social and political upheaval
557
how is a tuberculous granuloma formed? what is it made of?
- macrophages and lymphocytes are recruited to the alveoli due to inhaled MTB
- macrophages transform into epithelioid and Langhans cells; these aggregate with the lymphocytes to form the granuloma
558
what is a primary lesion/Ghon focus (TB)? how is it formed and where?
- a pale yellow, caseous nodule, few mm to 1-2 cm in diameter
- numerous tuberculous granulomas aggregate to form the primary lesion
- typically located in the periphery of the lung
- normal lung tissue is lost and replaced by a mass of fibrous tissue with granulomatous inflammation characterised by large numbers of macrophages and multinucleate giant cells
- central area of the focus shows caseous degeneration
559
where may MTB organisms spread to from the alveoli?
to hilar lymph nodes
560
what is the primary complex of Ranke?
- combination of primary lesion and regional lymph nodes
| - TB
561
what occurs in latent TB?
- reparative processes encase the primary complex in a fibrous capsule, limiting the spread of bacilli
562
what happens if there are no complications in TB?
- primary lesion calcifies and is clearly seen on a chest X-ray
563
how can primary lesions of TB spread? where can these secondary foci be seeded?
- lymphatic or haematogenous spread may occur before immunity is established
- lymph nodes, serous membranes, meninges, bones, liver, kidneys and lungs
- may lie dormant for years
564
what can reveal that there is a TB infection while it is dormant?
- appearance of a cell-mediated, delayed type hypersensitivity reaction to tuberculin; done by tuberculin skin testing
565
what are consequences of primary pulmonary TB?
1. spread from primary focus to hilar and mediastinal lymph glands to form the primary complex, which often heals spontaneously
2. direct extension of the primary focus; progressive pulmonary TB
3. spread to the pleura - tuberculous pleurisy and pleural effusion
4. blood-borne spread; few bacilli; pulmonary, skeletal, renal, GU infection, months or years later; massive spread - miliary TB and meningitis
566
what is primary pulmonary TB? when does clinical disease occur? when can it appear?
- infection of a previously uninfected (tuberculin negative) individual
- some patients may develop a self-limiting febrile illness
- clinical disease only occurs in there's a hypersensitivity reaction or progressive infection
- may appear during the course of the initial illness or after a latent period of weeks or months
567
what are the clinical features of miliary TB? what is it caused by?
- blood-borne dissemination gives rise to miliary TB
- may present acutely
- characterised by 2-3 weeks of fever, night sweats, anorexia, weight loss and a dry cough
- hepatosplenomegaly may develop
- headache may indicate coexistent tuberculous meningitis
- auscultation of the chest is often normal
- anaemia and leukopenia may reflect bone marrow involvement
568
what are appearances of miliary TB?
- auscultation of the chest is frequently normal, but in more advanced disease, widespread crackles are evident
- fundoscopy may show choroidal tubercles
- on X-ray, there are fine 1-2 mm lesions distributed throughout lung fields
569
what are patient-related factors increasing the risk of TB?
- age (children > young adults < elderly)
- first-generation immigrants from high prevalence countries
- close contacts of patients with smear-positive pulmonary TB
- overcrowding
- chest x-ray evidence of self-healed TB
- primary infection < 1 year previously
- smoking: cigarettes and bidis
570
what are associated diseases which increase the risk of TB?
- immunosuppression: HIV, anti-TNF therapy, high-dose corticosteroids, cytotoxic agents
- malignancy
- diabetes mellitus
- chronic kidney disease
- silicosis
- GI disease associated with malnutrition (gastrectomy, jejuno-ileal bypass, pancreatic cancer, malabsorption)
- vitamin D/A deficiency
- recent measles in children
571
what is natural history/manifestations of untreated primary TB for different times from infection?
3-8 weeks: primary complex, positive tuberculin skin test
3-6 months: meningeal, miliary and pleural disease
up to 3 years: GI, bone and joint, lymph node disease
around 8 years: renal tract disease
3 years onwards: post-primary disease due to reactivation or re infection
572
what are infection features of primary TB?
- 4-8 weeks
- influenza like illness
- skin test conversion
- primary complex
573
what are disease features of primary TB?
- lymphadenopathy: hilar (often unilateral), paratracheal or mediatinal
- collapse (esp. right middle lobe)
- consolidation (esp. right middle lobe)
- obstructive emphysema
- cavitation (rare)
- pleural effusion
- miliary
- meningitis
- pericarditis
574
what are hypersensitivity features of primary TB?
- erythema nodosum
- phlyctenular conjunctivitis
- dactylitis
575
what is cryptic TB? what are its features?
- age over 60 years
- intermittent low-grade pyrexia of unknown origin
- unexplained weight loss, general debility
- normal chest x-ray
- blood dyscrasias; leukaemoid reaction, pancytopenia
- negative tuberculin skin test
- confirmation by biopsy with granulomas and/or bacilli in liver or bone marrow
576
what is post-primary pulmonary TB? where does it often occur?
- exogenous (new infection) or endogenous (reactivation of a dormant primary lesion) infection in a person who has been sensitised by earlier exposure
- frequently pulmonary
- occurs in the apex of an upper lobe, where oxygen tension favours survival of the strictly aerobic organism
577
what is the onset and symptoms of post-primary pulmonary TB?
- onset is usually insidious, developing slowly over several weeks
- systemic symptoms include fever, night sweats, malaise, loss of appetite and weight and progressive pulmonary symptoms
- in extensive disease, there may be marked collapse and displacement of the trachea and mediastinum
- caseous lymph node may drain into an adjoining bronchus, leading to TB pneumonia
578
what are radiological changes in post-primary pulmonary TB?
- ill-defined opacification in one or both upper lobes
| - as progression occurs consolidation, collapse and cavitation develop to varying degrees
579
what is the incidence of extrapulmonary TB in individuals with/without TB?
- 20% of cases in those who are HIV negative
| - more common in HIV positive people
580
what is lymphadenitis?
- lymph nodes are the most common extrapulmonary site of disease
- cervical and mediastinal glands are affected most frequently, followed by axillary and inguinal, and more than one region may be involved
- disease may represent primary infection, spread from contiguous sites or reactivation
- supraclavicular lymphadenopathy is the result of spread from mediastinal disease
581
what are the physical signs of lymphadenitis?
- nodes are usually painless and initially motile but become matted together with time
- when caseation and liquification occur, the swelling becomes fluctuant and may discharge through the skin with formation of a collar-stud abscess and sinus formation
- half of cases fail to show any constitutional features, e.g. fevers or night sweats
582
what is the diagnosis/treatment of lymphadenitis?
- tuberculin test is usually strongly positive
- during or after treatment, paradoxical enlargement, development of new nodes and suppuration may occur without evidence of continued infection
- surgical excision is rarely necessary
- in non-immigrant children in the UK, it is mostly caused by opportunistic mycobacteria, esp. M.avium
583
what are some major manifestations of pulmonary TB?
- consolidation/collapse
- cavitation
- miliary diffuse shadowing
- pleural effusion/empyema
584
what are differential diagnoses of consolidation/collapse in pulmonary TB?
- pneumonia
- bronchial carcinoma
- pulmonary infarct
585
what are differential diagnoses of cavitation in pulmonary TB?
- pneumonia/lung abscess
- lung cancer
- pulmonary infarct
- Granulomatosis with polyangiitis (Wegener's granulomatosis)
- progressive massive fibrosis
586
what are differential diagnoses of miliary diffuse shadowing in pulmonary TB?
- sarcoidosis
- malignancy
- pneumoconiosis
- infection (e.g. histoplasmosis infection)
587
what are differential diagnoses of pleural effusion/empyema in pulmonary TB?
- bacterial pneumonia
- pulmonary infarction
- carcinoma
- connective tissue disorder
588
what are clinical presentations of pulmonary TB?
- chronic cough, often with haemoptysis
- pyrexia of unknown origin
- unresolved pneumonia
- exudative pleural effusion
- asymptomatic (diagnosis on chest x-ray)
- weight loss, general debility
- spontaneous pneumothroax
589
what are chronic pulmonary complications of pulmonary TB?
- massive haemoptysis
- cor pulmonale
- fibrosis/emphysema
- atypical mycobacterial infection
- aspergilloma
- lung/pleural calcification
- obstructive airways disease
- bronchiectasis
- bronchopleural fistula
590
what are chronic non-pulmonary complications of pulmonary TB?
- empyema necessitans
- laryngitis
- enteritis
- anorectal disease
- amyloidosis
- Poncet's polyarthritis
591
what is GI TB?
- TB can affect any part of the bowel
- upper GI involvement is rare and is usually an unexpected histological finding in an endoscopic or laparotomy specimen
- ileocaecal disease is half of abdominal TB cases
- fever, night sweats, anorexia and weight loss are prominent and a right IF mass may be palpable
- thickened bowel wall, abdominal lymphadenopathy, mesenteric thickening or ascites
- narrowing, shortening and distortion of the bowel, with caecal involvement
592
what is the diagnosis of GI TB? what is the histological/laprascopical appearance?
- histology by either colonoscopy or mini-laparotomy
- main differential diagnosis is Crohn's disease
- tuberculous peritonitis is characterised by abdominal distension, pain and constitutional symptoms
- ascitic fluid is exudative and cellular, with predominance of lymphocytes
- laproscopy reveals multiple white tubercles over the peritoneal and omental surfaces
- low grade hepatic dysfunction is common in miliary disease, where biopsy reveals granulomas
593
what is pericardial disease caused by TB? what are the symptoms?
- pericardial effusion and constrictive pericarditis
- presentation is usually insidious, with breathlessness and abdominal swelling
- coexistent pulmonary disease is very rare
- pulsus paradoxus, raised JVP, hepatomegaly, prominent ascites and peripheral oedema are common to both types
594
what are symptoms of pericardial effusion (TB)?
- associated with increased pericardial dullness and a globular enlarged heart on chest x-ray
- pericardial calcification occurs in 25% of cases
595
what are symptoms of constrictive pericarditis?
- associated with an early third heart sound and sometimes AF
596
what is the diagnosis of pericardial TB?
- based on clinical, radiological and echocardiographic findings
- effusion is frequently blood stained
- open pericardial biopsy can be performed where there is diagnostic uncertainty
597
how can pericardial TB be treated?
addition of corticosteroids to anti-TB treatment helps both forms of pericardial disease
598
what is CNS TB?
- meningeal disease is most important
- when unrecognised and untreated, it is rapidly fatal
- 30% mortality rates even when appropriate treatment is prescribed
- survivors may be left with neurological sequelae
599
what is bone and joint TB?
- spine is most common site for bony TB (Pott's disease); usually presents with chronic back pain and involves lower thoracic and lumbar spine
- infection starts as a discitis and spreads along the spinal ligaments to involve adjacent anterior vertebral bodies, causing angulation of the vertebrae with kyphosis
- paravertebral and psoas abscess formation is common and disease may prevent with a large abscess in inguinal region
600
how is bone and joint TB diagnosed?
- CT or MRI gauges the extent of disease, the amount of cord compression and site for needle biopsy or open exploration if required
- major differential diagnosis is malignancy, which affects the vertebral body and leaves the disc intact
601
what are features of joint TB?
- TB can affect any joint but most frequently involves the hip or knee
- presentation is usually insidious with pain and swelling; fever and night sweats are uncommon
- radiological changes are non-specific but reduction in joint space and erosions appear
- Poncet's arthropathy is an immunologically mediated polyarthrtis that resolves within 2 months of treatment
602
what are features of GU TB?
- fever and night sweats are rare with renal tract TB and patients are only mildly symptomatic for many years
- haematuria, frequency and dysuria are often present, with sterile pyuria found on urine microscopy
- in women, infertility from endometriosis, or pelvic pain and swelling from salpingitis or a tuboovarian abscess may occur
- in men, GU TB may present as epididymitis or prostatitis
603
what are systemic presentations of extrapulmonary TB?
- headache, vomiting, seizures, confusion, lymphocytic meningitis, hydrocephalus, tuberculoma
- chronic back pain, kyphosis, cord compression
- cranial nerve palsy, lymph node enlargment
- pericardial effusion, constrivtive pericarditis, abdominal mass, psoas abscess
- exudative ascites, mesenteric adenitis, intestinal obstruction
- haematuria/dysuria, infertility in women, epididymitis
- monoarthritis, anorectal ulceration
604
why are tuberculous bacilli difficult to stain?
substantial, lipid rich wall
605
what should prompt further investigation of possible TB?
- otherwise unexplained cough for more than 2-3 weeks, particularly in regions where TB is prevalent
- typical chest x-ray changes
606
what are the most effective techniques of staining tuberculous bacilli?
- Ziehl-Neelsen
- rhodamine-auramine: causes tuberculous bacilli to fluoresce against a dark background and is easier to use when there are multiple specimens to examine; more complex and expensive
607
how does MTB grow on different media?
- grows slowly and may take 4-6 weeks to appear on solid media
- 1-3 weeks in liquid media
608
what is the most accepted reference standard culture for MTB detection?
- radioactive BACTEC
- detects mycobacterial growth by measuring the liberation of 14^CO2, following metabolism of 14C-labelled substrate in the medium
609
how is drug sensitivity testing in TB diagnosis important?
- important in those with previous history of TB, treatment failure or chronic disease, those who are resident in or visited areas of high resistance, or who are HIV positive
- detection of rifampicin resistance, using molecular tools to test for rpo gene associated with 95% of rifampin resistant cases
- rifampin forms the cornerstone of 6-month chemotherapy
610
how are nucleic acid amplification tests used in diagnosing TB?
- e.g. Xpert/RIF test
- combine potential to diagnose TB and detect the presence of rifampin resistance
- may become first choice in individuals with HIV or those with multi drug resistant TB
- if a cluster of cases suggests a common source, confirmation may be produced by fingerprinting of isolates with restriction-fragment length polymorphism
611
how is extrapulmonary TB diagnosed?
- more challenging
- fewer organisms (esp. in meningeal or pleural fluid), so culture or histopathological examination of tissue is more important
- adenosine deaminase in pleural fluid/CSF may confirm TB
- in HIV, sputum examination is useful
612
what are the pulmonary specimens required in diagnosis of TB?
- sputum
- bronchoscopy with washings or BAL
- gastric washing
613
what are the extrapulmonary specimens required in diagnosis of TB?
- fluid examination (cerebrospinal, ascitic, pleural, pericardial, joint); yield classically very low
- tissue biopsy (from affected site): bone marrow/liver may be diagnostic in disseminated disease
614
what are diagnostic tests for TB?
- tuberculin skin test; low sensitivity/specificity; useful only in primary or deep-seated infection
- stain
- nucleic acid amplification
- culture
- pleural fluid: adenosine deaminase
- response to empirical antituberculous drugs (after 5-10 days)
615
what cultures are used in diagnosis of TB?
solid media: Loewenstein-Jensen, Middlebrook
| liquid media: BACTEC or MGIT
616
what is detected in pleural fluid in diagnosis of TB?
adenosine deaminase
617
what baseline blood tests are used in diagnosis of TB?
FBC, CRP, ESR, U&E and LFTs
618
what principle is the treatment of TB based on?
- initial intensive phase to reduce bacterial population rapidly
- followed by a continuation phase to destroy any remaining bacteria
619
what is standard treatment of TB?
- 6 months' treatment with isoniazid and rifampicin
- supplemented in first 2 months with pyrazinamide and ethambuol
- fixed dose tablets combining 2 or 3 drugs are preferred
620
when should TB treatment be commenced immediately?
patients who are smear-positive or smear-negative with typical x-ray changes and no response to standard antibiotics
621
when is TB treatment given for 12 months?
- meningeal TB and spinal cord TB
| - ethambutol may be replaced by streptomycin
622
when is pyridoxine prescribed for TB?
- pregnant women
- malnourished patients
- reduces the risk of peripheral neuropathy with isoniazis
623
when can TB patients be assumed to be non-infectious?
where drug resistance is not anticipated, after 2 weeks of appropriate therapy
624
what are the standard regimens for treatment of new TB patients (WHO recommendations)?
intensive phase: 2 months of isoniazid, rifampicin, pyrazinamide, ethambutol
continuation phase: 4 months of isoniazid and rifampicin
intensive phase: 2 months of isoniazid, rifampicin, pyrazinamide, ethambutol
continuation phase: 4 months of isoniazid, rifampicin and ethambutol
- applies in countries with high levels of isoniazid resistance in new TB patients, and where susceptibility testing is not done
625
what is the dosing frequency in treatment of new TB patients (WHO recommendations)?
intensive phase: daily
continuation phase: daily
- optimal
intensive phase: daily
continuation phase: 3 times/wk
- acceptable alternative for any new patient receiving directly observed therapy
intensive phase: 3 times/wk
continuation phase: 3 times/wk
- acceptable alternative, if patient is receiving directly observed therapy and doesn't have HIV or lives in a HIV prevalent setting
626
what are the first-line antituberculous drugs?
- isoniazid
- rifampicin
- pyrazinamide
- streptomycin
- ethambutol
627
what is the mode of action, major adverse reactions, and less common adverse reactions of isoniazid?
cell wall synthesis
major ADRs
- peripheral neuropathy
- hepatitis
- rash
less common ADRs
- lupoid reactions
- seizures
- psychoses
628
what is the mode of action, major adverse reactions, and less common adverse reactions of rifampicin?
DNA transcription
major ADRs
- febrile reactions
- hepatitis
- rash
- GI disturbance
less common ADRs
- interstitial nephritis
- thrombocytopenia
- haemolytic anaemia
629
what is the mode of action, major adverse reactions, and less common adverse reactions of pyrazinamide?
unknown
major ADRs
- hepatitis
- GI disturbance
- hyperuricaemia
less common ADRs
- rash
- photosensitisation
- gout
630
what is the mode of action, major adverse reactions, and less common adverse reactions of streptomycin?
protein synthesis
major ADRs
- 8th nerve damage
- rash
less common ADRs
- nephrotoxicity
- agranulocytosis
631
what is the mode of action, major adverse reactions, and less common adverse reactions of ethambutol?
cell wall synthesis
major ADRs
- retrobulbar neuritis
- arthralgia
less common ADRs
- peripheral neuropathy
- rash
632
when should admission to a hospital unit with appropriate isolation facilities be considered for TB patients?
most patients can be treated at home
- uncertainty about diagnosis
- intolerance of medication
- questionable treatment adherence
- adverse social conditions
- significant risk of MDR-TB (culture-positive after 2 months on treatment or contact with known MDR-TB)
633
what should patients treated with rifampicin be warned about?
- urine, tears and other secretions will develop a bright orange/red colouration
- women taking the oral contraceptive pill are warned that its efficacy will be reduced and alternative contraception may be necessary
634
why should baseline liver functioning be measured in patients treated with standard TB therapy?
- rifampicin may cause asymptomatic hyperbilirubinaemia, but along with isoniazid and pyrazinamide, may cause hepatitis
- mild asymptomatic increases in transaminases are common
- significant hepatotoxicity occurs in 2-5%
- less hepatotoxic regimens may be considered, e.g. streptomycin, ethambutol and fluoroquinolone
635
what effect can corticosteroids have on TB patients receiving treatment?
- reduce inflammation and limit tissue damage
- recommended when treating pericardial or meningeal disease, and in children with endobronchial disease
- may confer benefit in TB of the ureter, pleural effusions and extensive pulmonary disease
- can suppress hypersensitvity drug reactions
636
when should surgery be considered in TB treatment?
- massive haemoptysis, loculated empyema, constrictive pericarditis, lymph node suppuration and spinal disease with cord compression
637
how is effectiveness of pulmonary and extrapulmonary TB therapy assessed?
pulmonary TB
- further sputum smear at 2 months and at 5 months
- treatment failure is defined as a positive sputum smear or culture at 5 months or any patient with an MDR strain, regardless of smear results
extrapulmonary TB
- assessed clinically or radiographically
638
how do the WHO aim to control and prevent TB?
- reduce the incidence of TB by 2015
| - support the laboratory and health-care services to improve detection and treatment of active and latent TB
639
how is contact tracing used to detect latent TB?
- legal requirement in many countries
- can identify the probably index case, other cases infected by the same index patient and close contacts who should receive BCG vaccination or chemotherapy
- 10-20% of close contacts of patients with smear-positive pulmonary TB and 2-5% of those with smear-negative, culture-positive disease have evidence of TB infection
640
how are latent TB cases identified? when is chemoprophylaxis recommended?
- tuberculin skin test
- asymptomatic contact with a positive tuberculin skin test with a normal chest x-ray may be treated with chemoprophylaxis to prevent infection from progressing to clinical disease
- chemoprophylaxis is recommended for children under 16 who have a strongly positive tuberculin test, children under 2 in close contact with smear-positive pulmonary disease, where recent tuberculin conversion has been confirmed, and babies of mothers with pulmonary TB, and for HIV-infected close contacts of a patient with smear positive disease
641
what are some limitations of tuberculin skin testing?
- may be associated with false positive reactions in those who have had a BCG vaccination and in areas where exposure to non-tuberculous mycobacteria is high
- may be falsely negative in setting of immunosuppression or overwhelming infection
642
how do interferon gamma release assays work? what are some advantages of them?
- measure the release of IFN-gamma from sensitised T cells in response to antigens, e.g. early secretory antigenic target (ESAT)-6 or culture filtrate protein (CFP)-10
- these antigens are encoded by genes specific to MTB and are not shared with BCG or opportunistic mycobacteria
- greater specificity and only require one blood tests as opposed to two visits for skin testing
643
what samples are used for interferon-gamma release assays?
purified T lymphocytes or whole blood
644
what is the process of interferon-gamma release assays for both types of sample?
purified T lymphocytes
1. incubate in presence of antigens specific to MTB
2. IFN-gamma released
3. IFN-gamma binds to antibody on base of ELISPOT wells
4. spots counted
whole blood
1. incubate in presence of antigens specific to MTB
2. IFN-gamma released
3. supernatant removed and IFN-gamma measured by ELISA
645
what are skin tests for TB that use purified protein derivatives?
Heaf test and Mantoux test
646
what is the Heaf test?
- TB skin test
- read at 3-7 days
- multipuncture method: Grade 1: 4-6 papules; Grade 2: confluent papules forming ring; Grade 3: central induration; Grade 4: > 10 mm induration
647
what is the Mantoux test?
- TB skin test
- read at 2-4 days
- 10 tuberculin units used
- positive when induration 5-14 mm and more than 15 mm
648
when do false negatives occur in TB skin tests using PPD?
- severe TB (25% of cases negative)
- newborn and elderly
- HIV (if CD4 count < 200 cells/mL)
- malnutrition
- recent infection or immunisation
- immunosuppressive drugs
- malignancy
- sarcoidosis
649
what is directly observed therapy for TB? when is it used?
- poor adherence to therapy is a major factor in prolonged illness, risk of relapse, emergence of drug resistance
- DOT involves supervised administration of therapy 3 times weekly to improve adherence
- important control strategy in resource poor nations
- in UK, it is recommended for homeless people/drifters, alcohol or drug users, patients with serious mental illness and those with history of non-compliance
650
what is the link between TB and HIV/AIDS
- close links between them, esp. in Saharan Africa, and the potential for both diseases to overwhelm health care funding in resource poor nations has been recognised
- promotion of programmes with link detection and treatment of TB and HIV
- recommended that all patients with TB should be tested for HIV
- mortality is high and TB is a leading cause of death in HIV patients
651
what is drug resistant TB/ MDR TB?
- drug resistant TB is the presence of resistance to any first line agent
- MDRTB is resistance to at least rifampicin and isoniazid, with or without other drug resistance
- extensively drug-resistant TB (XDR-TB) is resistance to at lease rifampicin and isoniazid, in addition to any quinolone and at least one injectable second line agent
- prevalence of MDR-TB is rising, and is more common in those with prior history, if treatment has been inadequate and those with HIV infection
- mortality rate from MDR-TB is high, and that from XDR-TB higher still
652
what are vaccines used against TB?
- BCG (live attenuated vaccine derived from M. bovis) is the most established TB vaccine
- administered by intradermal injection, highly immunogenic
- effective in preventing disseminated disease, including TB meningitis
- efficacy in adults is inconsistent
653
what are factors contributing to the emergence of drug-resistant TB?
- drug shortages
- poor quality drugs
- lack of appropriate supervision
- transmission of drug resistant strains
- prior anti-TB treatment
- treatment failure (smear positive at 5 months)
654
what is the prognosis of TB?
- after chemotherapy, most patients are cured
- small and unavoidable risk of relapse, occurring within 5 months
- without treatment, a patient with smear-positive TB remains infectious for an average of 2 years; in 1 year, 25% of untreated cases will die
- death more likely in those who are smear-positive and those who smoke
- some die unexpectedly soon
- HIV positive patients have higher mortality and increased risk of relapse
655
what sites are commonly affected by environmental/atypical mycobacteria?
lungs, lymph nodes, skin and soft tissues
656
what diagnostic systems can be used for opportunistic mycobacterial infection?
- DNA probes
- high-performance liquid chromatography
- PCR restriction enzyme analysis
- 16S rRNA gene sequence analysis
657
what patients are affected by opportunistic mycobacterial infection?
- HIV patients
- COPD
- bronchiectasis
- pneumoconiosis
- old TB
- CF
658
what are the most commonly reported organisms causing opportunistic mycobacterial infection?
M. avium, M. kansasii, M. malmoense, M. xenopi, M. abscessus, M. fortuitum
659
what organisms cause pulmonary opportunistic mycobacterial disease?
- M. xenopi
- M. kansasii
- M. malmoense
- M. avium complex
660
what organisms cause lymph node opportunistic mycobacterial disease?
- M. avium complex
- M. malmoense
- M. fortuitum
- M. chelonei
661
what organisms cause soft tissue/skin opportunistic mycobacterial disease?
- M. leprae
- M. ulcerans
- M. marinum
- M. fortuitum
- M. chelonei
662
what organisms cause disseminated opportunistic mycobacterial disease?
- M. avium complex (HIV associated)
- M. haemophilum
- M. genavense
- M. fortuitum
- M. chelonei
- BCG
663
what are types of Leishmaniasis?
- cutaneous leishmaniasis
- mucocutaneous
- visceral leishmaniasis 'Kala Azar'
664
what does T. vaginalis lead to in women and men?
women: purulent discharge, abdominal pain, dysuria, vulvar/cervical lesions and dysparenurea
665
what is the vector for malaria?
female enophales mosquito
666
why do maleria symptoms occur?
1. parasite develops in the RBC producing waste products and toxic factors
2. infected cells lyse releasing merozoited, surface proteins and hemozoin into the blood
3. stimulates macrophages to release inflammatory cytokines
