Microbiology Flashcards
1
Q
What is herpes simplex encephalitis caused by?
A
Most common cause of sporadic encephalitis in the Western world
Most common in childhood on primary infection with HSV-1
Inborn errors in at least 6 genes are implicated in HSE= TLR3,UNC93B1,TRIF, TRAF3,TBK1 and IRF3
These impair the CNS’ intrinsic interferon alpha/beta response to HSV infection
Virus replicates to a much higher extent than it would otherwise have done
2
Q
What is interferon?
A
Transferable factor
Produced when cells are exposed to a virus
It binds to specific receptors and signals activation of de novo transcription of hundreds of Interferon Stimulated Genes
3
Q
What is the overall response to a virus?
A
Intrinsic
Innate immunity
Acquired immunity
4
Q
What are ISGs?
A
Interferon stimulated genes
5
Q
What are type I interferons? How do they work?
A
Polypeptides secreted from infected cells-> recruit APCs and adaptive immune cells
BETA FIRST
Sense a viral infection and make an interferon response-> synthesis of new copies of IFN-beta (the first interferon to be made)
IFNb is secreted from these cells and diffuses to neighbouring cells (to interact with receptors)
Genes in neighbouring cells switched into an anti-viral state
ALPHA SECOND
PDCs make interferons (particularly IFN-alpha)
6
Q
What are the major functions of type I interferons?
A
Induce antimicrobial state in infected and neighbouring cells
Modulate innate response to promote Ag presentation and NK but inhibit proinflammation
Activate the adaptive immune response
7
Q
What are PDCs?
A
Plasmacytoid dendritic cells
Specialised cells that are very good at making interferon (particularly IFN-a)
Constitutively express high levels of IRF-7
8
Q
What are the Type I interferons?
A
IFN alpha and IFN beta
9
Q
What triggers IFNbeta induction?
A
IRF-3
10
Q
What interferon do all cells secrete?
A
IFN beta (type I)
11
Q
What interferon receptor is present on all tissues?
A
IFNAR
12
Q
What genes code for IFN beta and IFN alpha?
A
IFN B= one gene
IFN a= 13/14 isotypes
13
Q
What is the Type II interferon?
A
IFNy
14
Q
What produces IFNy? How does it signal?
A
Produced by activated T cells and NK cells
Signals through a different receptor IFNGR
15
Q
What is the Type III interferon? Where are they important?
A
IFN lambda (important at epithelial surfaces)
16
Q
How does Type III interferon signal?
A
Signals through receptors IL28R and IL10 beta that are mainly present on epithelial surfaces
17
Q
What are polymorphisms in the IFN lambda important for?
A
Different outcomes from liver viruses e.g. Hep B and Hep C
Some people can spontaneously clear the virus (and some don’t react to antivviral therapy)
18
Q
How are pathogens sensed (identifying self from non self)?
A
PAMPs e.g. ssRNA
PRRs e.g. RLRs
Sense foreign nucleic acids
19
Q
What are PAMPs?
A
Pathogen associated molecular patterns
20
Q
What are PRRs?
A
Pattern recognition receptors
21
Q
What kinds of receptors sense the presence of viruses? Where are they?
A
RLRs= RIG-I like receptors
- Cytoplasmic (then signal through mitochondrial located pathway)
TLRs= Toll like receptors
- Plasma membranes and endosomal membranes
NLRs= Nucleotide oligomerisation domain receptors
- Cytoplasmic
DNA sensors e.g. cGAS (signals to a molecule called STING on the ER)
22
Q
How are interferons induced?
A
PRRs (e.g. RLRs) detect PAMPS e.g. ssRNA in cytoplasm of cell
RIG-1 signals through Mavs (on mitochondrion)-> signalling through different pathways-> translocation of molecules from cytoplasm to nucleus
TFs become phosphorylated and bind to promoter regions of target genes (IFNbeta) and generate IFN beta transcripts
IFNb then released-> travel to neighbouring cells to induce anti-viral state
23
Q
How are TLRs and cytoplasmic sensors involved in virus infection?
A
Virus enters cells and becomes inside endosome
Nucleic acids are exposed inside the endosome
(NB. In a normal healthy cell shouldn’t be any nucleic acids inside the endosomes)
TLRs sense the nucleic acids in endosome and signal to MyD88 molecule outside the endosome-> various TFs sent to nucleus of the cell-> switch of expression of IFNalpha
24
Q
What is the main way DNA viruses are sensed?
A
cGAS
25
What is cGAS?
Involved in DNA virus sensing
Enzyme that binds to dsDNA in the cytoplasm and synthesises a 2nd messenger (cGAMP)
26
Outline the pathway of cGAS
cGAS binds to dsDNA in the cytoplasm and synthesises a 2nd messenger (cGAMP)
This small dinucleotide diffuses to a protein called STING on ER
Triggers phosphorylation of signalling molecules/TFs (same as RNA viruses trigger)
-> STING is a central player in IFN induction through cGAS
27
True or false: IFN is a soluble cytokine
True
28
What is the structure of the IFN receptors?
Heterodimers of IFNAR1 and IFNAR2
Upon binding to cell surface R-> IFNB secreted and diffuses to receptor on another cell (warns cell that virus is coming so antiviral/ interferon signals can be started)
29
What can the IFN receptor sense?
IFN alpha and beta
30
What happens when IFN binds to the IFN receptor?
Activates Jak and Tyk-> pshoprylate STAT molecules (STAT1 and STAT2)
STAT molecules dimerise and combine with IRF9-> goes to nucleus and binds to a promoter region that is responsive to that TF
31
List interferon stimulated genes
```
PKR
2’5’OAS
Mx
ISG15, ISG54, ISG56
PML bodies
APOBECs and TRIMs
ADAR
Serpine
Viperin
miRNAs
Apoptosis
Cell cycle arrest
```
32
What role does IFITM3 have on endosomes?
Sits on membrane of endosomes in cells that have been previously stimulated with interferon
Restricts virus entry through endosomes
(Stops virus being able to escape)
Virus gets trapped in endosome because membrane of endosome has been modified
Virus can’t fuse its membrane with endosomal membrane and release its genome into the cell
33
What is IFITM3?
Interferon induced transmembrane protein 3
34
What happens to people and mice lacking IFITM3?
Get more severe influenza
35
What is Mx?
GTPase with homology to dynamic
Antiviral mediator
Can form multimers that wrap around nucleocapsids of incoming viruses -> blocks their intracellular transport
Mx1 and Mx2
36
What does Mx1 inhibit?
Influenza
37
What does Mx2 inhibit?
HIV
38
How long does the antiviral state last?
Doesn't last
Maintained for several hours
Subsequently lose ability to respond to IFN due to negative regulation
SOCS suppressor of cytokine signalling genes turn off the response
39
How can viruses evade immune response?
Hiding the PAMP
Interfere globally with host cell gene expression and/or protein synthesis
Block IFN induction cascades by destroying or binding
Inhibit IFN signalling
Block the action of individual IFN induced antiviral enzymes
Activate SOCS
Replication strategy that is insensitive to IFN
40
How do interferons control the hep C virus?
STOP ACTIVATION
NS3/4 protease acts as antagonist to interferon induction by cleaving MAVS
HOW?
- MAVS important in detecting Hep C through the RIG-1 pathway (and switching on IFN response)
- Causes destruction of the sensor system by cleaving mAVS away from the mitochondrion and preventing the signal from getting through
41
How do interferons control the influenza virus?
STOP ACTIVATION
NS1 protein acts as antagonist to interferon induction by binding to RIG-I /TRIM25/RNA complex and preventing activation of signalling pathway
Also prevents nuclear processing of newly induced genes
HOW?
Acts at an early stage in detecting viral RNA
Prevents nuclear processing of newly induced genes
42
What kind of viruses are pox viruses?
Large DNA viruses
| More than half is accessory genes that modify the immune response
43
What do pox viruses do?
Encode soluble cytokine receptors (vaccinia virus B18) which mops up IFN and prevents it ever reaching it's receptor
44
How does ebola counteract our immune response?
Encodes 2 proteins (VP35 and VP24)
```
VP35= inhibits the RIG-I pathway
VP24= stops the signal from getting through from the IFNb receptor to the nucleus (stops STAT1 molecules from getting to the nucleus)
```
The virus can continue to replication unchecked and accumulate because patient is unable to amount a proper immune response
45
What are the consequences of innate immunity in viral pathology?
Damaged infected cells by virus and damaged infected/bystander cells by the immune response
Virus coevolves with host to have a set of its own genes
Balance between these two things determines viral load and outcome of the infection
46
Why do viruses modulate the immune response?
To increase their own replication and transmission-> can lead to pathology
47
How can an interferon be immunopathology?
If you make too much of it
48
What is the cytokine storm in virus infections?
Virus replication-> induces high levels of IFN accompanied by massive release of TNF alpha and other cytokines
May affect clinical results of patients (depending on innate immune system- maybe affected by age)
Cytokines are very damaging-> pulmonary fibrosis (accumulation of immune cells in the lung spaces)
Patient can die from immune pathology rather than direct damage from the virus
49
What viruses commonly cause cytokine storms?
Dengue haemorrhagic fever
Sever influenze infections
Ebola
50
Why are viruses that lack the ability to control interferon useful as live attenuated vaccines?
Viruses deficient in control of IFN are attenuated in IFN competent cells
The high IFN levels they induce can also recruit useful immune cells, IFN acting as an ‘adjuvant’
Useful in vaccine because live virus can be injected into host and won’t replicate enough to cause disease but will replicate enough that other parts of the immune system can recognise it as being foreign-> immunological response and immunological memory
51
What is the downside of engineering a virus that lacks the ability to control interferon for a live attenuated vaccine?
No longer a fit virus so difficult to propagate the virus sufficiently to produce enough virus for loads of vaccines
Won't grow very well in healthy cells
Culture cells can be genetically engineered to be deficient in the IFN response
Deficient virus can replicate in the deficient cells
52
Why can't interferon be the first 'broad spectrum antiviral'?
E.g. pegylated IFN with ribavirin to treat Hep C
Several unpleasant side effects
Stimulated the production of several cytokines (e.g. TNFa and IL6)
53
Could IFN lambda be used as an influenza therapeutic?
Active on receptors present on epithelial surfaces
Can't signal through receptors present on immune cells (unlike type 1 interferon which can lead to immunopathology making patient feel sick)
Can induce antiviral state in target cells without knock-on SEs of immunopathology and inflammatoin
54
Why is the IFN deficient state of cancer cells important for viruses?
Oncolytic viruses take advantage
Cancer cells are deficient in their ability to mount a proper response
55
Which is not true:
Viruses that can’t control the innate immune system well might….
A: be useful as oncolytic agents
B: be difficult to grow in standard cell culture systems
C: be restricted at crossing the host range barrier and unlikely to spark outbreaks in other species
D: be useful as live-attenuated vaccines
E: be highly adapted to their host species
E: be highly adapted to their host species
56
Which is true:
Viruses counteract activation of the innate immune system by:
A: varying their coat protein sequences
B: encoding proteins that cleave or target host immune factors for degradation
C: preventing the loading of peptides by TAP
D: inducing a cytokine storm
E: encoding MHC homologues
B: encoding proteins that cleave or target host immune factors for degradation
57
What kind of climate leads to high rates of skin infections?
Hot, humid condiitons and poor populations
58
What is staphylococcus aureus?
Gram positive bacterium
Commensal in 30% humans (colonises nose, axillae and groins)
59
What can s. aureus cause?
Most common bacterial cause of skin infections (impetigo, folliculitis, ecthyma, boils and carbuncles)
Produces toxins so can lead to:
- Staphylococcal scalded skin syndrome (exfoliative toxin)
- Toxic shock syndrome (TSS toxin 1)
- Food poisoning (enterotoxin)
- Necrotising soft tissue infections (panton valentine leucocidin virulence factor)
Can cause bone, joint and lung infections and sepsis
(Treated with antibiotics)
60
What is impetigo? Clinical features
Infection of subcorneal layer of epidermis
Usually around mouth and nose
Crusted erosion
Often children and young people
S. aureus often makes gold colour
Can have bullous impetigo
61
What is folliculitis?
Infection of mouth of hair follicle
62
What is ecthyma?
infection of full thickness of epidermis
63
What is a boil?
Abscess of hair follicle
Doesn't respond well to antibiotics (can excise and get puss out)
64
What is a carbuncle?
Abcess of several adjacent hair follicles
65
What happens in staphylococcal scalded skin syndrome?
Staph infection leads to exfoliative toxin
| Cleavage and skin scalds off
66
What is treponema pallidum?
```
Gram negative spirochaete
Cause of Syphilis
Sexually transmitted disease
12 million new cases per year worldwide
Increases transmission of HIV
```
67
What are the types of syphilis?
```
Primary (3-8 weeks)
Secondary (6-12 weeks)
Latent
Tertiary
Congenital
```
68
How is syphilis treated?
No vaccine available but can treat with antibiotics
69
What is primary syphilis?
3-8 weeks
| Painless ulcer at inoculation site (genital or oral)
70
What is secondary syphilis?
6-12 weeks
Disseminated infection
Generalised rash and lymphadenopathy
71
What are the signs of latent syphilis?
No clinical signs
72
What is tertiary syphilis?
Usually years later
| Skin, neurological and vascular manifestations
73
What is congenital syphilis?
Vertical transmission
Acquired perinatally
Early and late manifestations (broad range)
74
What is a chancre?
Painless ulcer, particularly one that develops on the genitals in venereal disease
75
What kinds of rashes of secondary syphilis are there?
Maculopapular rash
Condyloma lata
Palm and soles involvement
76
What are the clinical symptoms that tertiary syphilis can cause?
Gummatous skin lesions
Bone lesions
Thoracic aneurysm
Neurosyphilis
77
What can congenital syphilis cause?
```
Miscarriage
Still birth
Prematurity
Rashes
Brain and neurological problems
Bone disease
```
78
How is herpes virus transmitted?
Transmission by direct contact (e.g. kissing and sex)
79
What kind of viruses are herpes viruses?
DNA virus
80
What do type 1 and 2 herpes viruses cause?
Type 1= HHV-1= usually causes oral infections
Type 2= HHV-2= usually causes genital infections
Type 3= VZV= Chickenpox or shingles
All target muco-epithelial cells and site of latency is neurons
81
What are the clinical features of herpes?
Clinical infection results in a painful vesicular rash which heals over 2-4 weeks
Eczema herpeticum
Herpes encephalitis
Due to latency in sensory neurons, there can be reactivation with recurrences of infection
Outbreaks can be treated with anti-viral medication such as acyclovir
82
What is varicella zoster?
A human herpes virus
Primary infection causes chicken pox (prodrome of fever and malaise followed by vesicular rash- lasting about 2 weeks)
Latent in sensory neurons and can reactivate to cause Herpes Zoster (shingles)
83
What is shingles?
Herpes zoster
Where reactivation of VZV and a painful vesicular rash appears only along course of a dermatome (sensory nerve)
2-4 weeks
Serious eye consequences in ophthalmic division of trigeminal nerve is involved
84
Can you vaccinate against shingles?
Anti-viral medication e.g. acyclovir can be prescribed
85
Give examples of superficial skin fungal infections
Dermatophytes (mould grows in keratin, long hyphae and grow from tip) e.g. trichophyton rubtrum
Yeasts (grow on warm, wet surfaces, single cell and bud) e.g. candida
86
What is trichophytum?
Mould (dermatophyte) causing superficial fungal infections
Infects parts of the body with keratin e.g. skin, nails and hair
Causes clinical infections with prefix 'tinea'
Common species= trichophytum rubrum
87
What are the clinical manifestations of trichophytum?
Erythematous scaly rash on skin or scalp
Discoloured and crumbly nails
Can be treated with topical or systemic antifungal medication (e.g. terbinafine)
88
What is tinea unguium?
Trichophytum infection of toe nail
Often asymptomatic apart from appearance
Antifungal treatment (can take a long time to grow out)
89
What is tinea capitis?
Trichophytum infection of scalp
Normally only affects children
Different types e.g. kerion
90
What is tinea manuum?
Trichophytum infection of hand
91
What is tinea pedis?
Trichophytum infection of foot
92
What is tinea cruris?
Trichophytum infection of groin
93
What is tinea facei?
Trichophytum infection of face
94
What is candida intertrigo?
Superficial skin infection caused by yeast
E.g. under breast
Can be treated with topical antifungal treatment
95
What is scabies? What does it cause?
Skin infestation with mite Sarcoptes Scabei
Mite burrows into surface of skin (scabetic burrows)
Mite faeces and eggs cause delayed allergic reaction-> widespread eczematous rash (very itchy) about 4 weeks after infestation
96
Where are common sites of scabetic burrows?
Genital region, nipples, wrists, finger webs, instep of the feet and axillae
NB. Patient sometimes scratches too much to see the burrows
Secondary bacterial infection is common
97
Why are viruses easy targets for processing and presentation by MHC?
Intracellular pathogens
| Proteins are easy targets
98
Why are internal viral protein important targets of cellular immunity?
Tend to vary less than surface antigens
99
How can an antigen evade MHC class 1 presentation and the presentation cycle?
Evasion of antigen loading to TAP
Modulation of tapasin function and prevention of MHC transport
Interfering with MHC presentation at the cell surface
100
How do viruses evade antigens loading to TAP?
3 different herpes viruses have different ways of stopping the TAP part of the presentation cycle
```
EPSTEIN BARR VIRUS EBNA1 (EBV antigen 1)
Have modifications (glycine and alanine repeats) that can't be processed by proteasome
```
HSV ICP47
Blocks access of the processed peptide to TAP
CMS US6
Stops ATP binding to TAP
Prevents translocation
101
How do viruses modulate tapasin function to prevent MHC transport?
CMV US3
Binds tapasin and prevents peptides being loaded to MHC
ADENOVIRUS E3-19K
Prevents recruitment of TAP to tapasin and retains MHC in the endoplasmic reticulum
102
How do viruses interfere with MHC presentation at the cell surface?
KSHV (Kaposi sarcoma herpes virus) kK3
kK3 protein induces polyubiquitinylation and internalization of MHC (stop presentation at surface)
From internalized endosome, MHC is passed to lysosomes where it is degraded
103
How do viruses avoid NK killing?
Miss the self mechanism
Normal healthy cells display MHC at their surface but those that don't are detected by NK cells and killed
Viruses can encode MHC analogues or upregulate MHC so they don't get killed
104
What needs to happen to manipulate the HCMV infection in transplant recipients?
Need to eliminate it from bone marrow cells of a transplant recipient before transplantation (so it can't reactivate)
Quantative proteomics used
UL138 protein encoded by the virus to get rid of the transporter molecule
Leads to loss of MRP-1 (which transports toxic substances out of the cell)
Loss of MRP-1 -> accumulation of certain molecules including vincristine (toxic drug
Vincristine-treat cells from donors first (builds up in infected cells and can kill them)
105
What is antigenic variation?
The mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its surface proteins in order to evade a host immune response
Driven by antigenic pressure from host (influenza antigenic drift, HIV quasispecies)
New subtypes are introduced (influenza antigenic shift)
Exist as different genetically stable serotypes that co-circulate in humans (rhinovirus, poliovirus and dengue)
Consequence for vaccination
106
What drives influenza antigenic change?
Evolutionary pressure
107
What is antigenic drift?
Mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites
108
How does antigenic drift affect influenza vaccinations?
Vaccines need to be updated every year to best represent the circulating strains
109
What do flu vaccines protect against?
Flu vaccines were designed to protect against three different flu viruses (trivalent) or four different flu viruses (quadrivalent)
110
Why did the 2014/2015 flu vaccine have low efficacy?
Selected strain was a poor match with the predominant circulating virus
111
How could a universal flu vaccine be developed?
Previously flu vaccines have only targeted variable region
Can make antibodies to stem/stalk (only recently discovered this)
Conserved region doesn’t vary so maybe we could make body able to produce ‘broadly neutralising antibodies’ (stem antibodies) to target stem
Wouldn’t need to update vaccine every year
112
Why do antibodies evade HIV?
HIV envelope has gp120 HIV spike that resists neutralization
Large space between spikes prevent antibody cross-linking
Extensive glycosylation (sugar cloud) masks antibody epitopes (AAs can't be seen)
Functionally important parts of molecule are poorly accessible (CD4 binding site, redundant AAs are visible to B cell receptor and antibodies)
Huge variation in redundant AAs so most antibodies are clade specific
113
How do broadly neutralizing antibodies fight HIV?
Antibodies bind to many parts of gp120
Broadly neutralise
Some people have this naturally (control HIV viral load for a while)
Could be used as biological therapeutics
Viral load controlled by BNabs but escape mutants do appear
114
How many antigenically distinct serotypes of human rhinoviruses are there?
120
| Co-circulate
115
What was the poliovirus vaccine based on?
Trivalent (because 3 serotypes of poliovirus)
116
What happens if all 3 serotypes of poliovirus are administered at once?
Live attenuated Sabin vaccine
| Virus interference and poor response to one component
117
Why is Dengue virus re-infection so serious?
4 different serotypes
Antibody generated against a previous infection can bind but not neutralise (leads to ADE which causes dengue haemorrhagic fever)
```
Make antibodies for 1st type they are exposed to
If infected with another type- antibodies already made make it worse (enhancement)
Antibody binds to virus
FC receptors (displayed on immune cells)- can be used as new entry mechanism e.g. to infect monocytes-> triggers cytokine storm-> increases viral load and causes endothelial leakage and capillary destruction
```
118
What happens in Dengue virus?
Dengue causes leakage of blood plasma from capillaries
Detected by increase in RBCs and decrease in protein level in blood
Tendency to severe bruising, and bleeding
Patient deteriorates even after fever drops, shock
Treat with iv fluid replacement
119
Give two examples of viruses with glycoprotein antigens that are heavily glycosylated. Why is this useful?
HIV and ebola
Mucin like glycosylation
Antibody access is hindered
Evade antibody response
120
How does ebola evade antibody surveillance with phosphatidyl serine lipids?
Ebola virus particle membranes have a high content of phosphatidyl serine lipids
This makes them look like apoptotic bodies that are rapidly taken up by macropinocytosis, away from antibody surveillance
121
What do viral filaments do to help evade the antibody response?
Viral filaments might be harder for antibodies to neutralize as GP inaccessible in folded pockets (EBOV)
122
What is sGP and what is it's role in ebola evasion?
Soluble GP is the default coding for the GP gene
Full length GP is made by polymerase stuttering
sGP is an antibody decoy= immunosuppressive, inhibits neutrophils
(Reston virus version only suppressive in macaques)
123
What is unusual about the measles vaccination?
Has a much larger impact on childhood mortality than expected if it only protect against measles virus itself
MV infects CD150 positive cells, including memory lymphocytes and erases immunological memory
Leads to decreases morbidity and mortality from other diseases
124
Which is true?
RNA viruses are more likely than DNA viruses to:
A: Code for proteins that interfere with innate immunity
B: Code for proteins that interfere with cellular immunity
C: Have error prone polymerases that promote antigenic variation
D: Use lipid envelopes to protect their genomes that also contain host proteins that control complement activation
E: Activate interferon induction pathway through cGAS and STING
C: Have error prone polymerases that promote antigenic variation
125
Which is NOT true:
Hepatitis C virus evades our immune systems in the following ways:
A: Its E2 protein varies by more than 30% so antibodies only bind a tiny fraction of the viral quasispecies
B: T cell epitopes vary so that the virus is not cleared in the early stage of infection and this determines chronicity
C: NS3/4A protease cleaves MAVS and prevents activation of interferon
D: It encodes a protein called vif that counteracts the interferon stimulated gene APOBEC and prevent it from inducing hypermutation of the viral genome
E: A genetic polymorphism in IL28b results in non-responsivenes to interferon treatment
D: It encodes a protein called vif that counteracts the interferon stimulated gene APOBEC and prevent it from inducing hypermutation of the viral genome
126
What forms do bacteria come in?
```
COCCI
Coccus
Diplococci
Steptococci
Sarcina
Tetrad
Staphylococci
Diplococci encapsulated (pneumococcus)
```
```
BACILLI (rods)
Coccobacillus
Bacillus
Diplobacilli
Palisades
```
BUDDING
Hypha and stalk
```
OTHER
Enlarged rod fusobacterium
Vibrio
Comma's form (b dellovibrio)
Club rod (corynebacteriacaeae)
Helical form (h. pylori)
Corkscrew's form (borrelia burgdorferi)
Filamentous
Spirochete
```
127
What are the components of bacterial cells?
```
Capsule
Plasma membrane
Cell wall
Cytoplasm
Pili
DNA
Flagellum
Ribosomes
```
128
What virulence factors do bacteria have?
Diverse secretion systems
Flagella= movement, attachment
Pili= important adherence factors
Capsules= to protect against phagocytosis
Endospores= metabolically dormant forms that resist heat, cold, desiccation and chemicals
Biofilms= antibiotic resistant aggregates
Exotoxins
129
What are exotoxins?
Toxin secreted by bacteria
Can cause damage to the host by destroying cells or disrupting normal cellular metabolism
May be secreted, or, similar to endotoxins, may be released during lysis of the cell
130
What are the kinds of exotoxins?
```
Neurotoxins
Enterotoxins
Pyrogenic exotoxins
Tissue invasive exotoxins
Mischellaneous exotoxins
```
131
What do enterotoxins do? Examples.
Local enterotoxin bind to GI tract (activate NaCl secretion or kill intestinal epithelial cells-> common end result= osmotic pull of fluid into intestine-> diarrhoea)
E.g. vibrio cholera, escheria coli, shigella dysenteriae, campylobacter jejuni
Also in food poisoning (bacteria from food release enterotoxins)
E.g. bacillus cereus or staph aureus
132
What do pyrogenic exotoxins do? Examples.
Stimulate release of cytokines
| E.g. staph aureus or stept pyogenes
133
What do tissue invasive exotoxins do? Examples.
Allow bacteria to destroy and tunnel through tissue (enzymes destroy DNA, collagen, fibrin, NAD, WBCs or RBCs)
E.g. staph aureus, strept pyogenes, clostridium perfringens
134
What do miscellaneous exotoxins do? Examples.
Specific to a certain bacteriumor function not well understood
E.g. bacillus anthracis and corynebacterium diphtheriae
135
What are endotoxins?
Produced by gram-negative bacteria
Lipid A moiety of LPS
Shed in steady amounts from living bacteria
136
What is the danger with endotoxin treatment?
Treating a patient with gram negative infection with antibiotics can worsen condition
Bacteria lyse-> release large quantities of LPS (endotoxin) -> septic shock
Lung, abdomen and urinary tract are common places
137
What is septic shock?
Sepsis that results in dangerous drops in blood pressure and organ dysfunction
Also known as endotoxin shock
138
What is an outbreak?
An outbreak is a greater-than-normal or greater-than-expected number of individuals infected or diagnosed with a particular infection in a given period of time, or a particular place, or both
139
How can an outbreak be identified?
Surveillance provides an opportunity to identify outbreaks
| Good and timely reporting systems are instrumental to identify outbreaks
140
What was an important microbe outbreak in Europe in recent years?
2011 e. coli outbreak in Germany (and then small outbreak in France)
Entero-aggregative shiga-toxin producing e. coli strain
Lead to gastroenteritis and hemolytic-uremic syndrome
Probably caused by sprouts
3816 cases with 54 deaths
141
What is hemolytic-uremis syndrome?
HUS
142
What is hemolytic-uremis syndrome?
HUS
Triad= acute renal failure, hemolytic anemia and thrombocytopenia
Usually in children and cause by shiga toxin producting e.coli strain (enterohemorrhagic EHEC strain)
Cattle and other ruminants often reservoir
Human infection occurs through the inadvertent ingestion of fecal matter and secondary through contact with infected humans
143
How can PCR be used in outbreaks?
To detect outbreak strain
Isolates can be screened by multiplex PCR for characteristic features of the outbreak strain
Can be done on stool samples
144
In the 2011 Germany outbreak, what did pCR show about the e. coli?
EAHEC STRAIN (pAA plasmid from EAEC and STX phage from EHEC)
Isolate similar to enteroaggregative e. coli (EAEC)
- pAA-type plasmids of EAEC strains, which contains the aggregative adhesion fimbrial operon
- ESBL plasmid: harbours the genes encoding for extended-spectrum β-lactamases
Main significant difference of the outbreak strain to those of EAEC strains is the presence of a prophage encoding the Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC) strains
145
How does the shiga or vero toxin work?
AB5 subunit composition
Subunit A (StxA)= non-covalently associated with pentamer of StB
Has enzymatically active domain (from StxA) and StxB pentamer for binding to host cell Rs
StxA enzyme cleaves the 28s rRNA in eukaryotic cells-> leads to inhibition of protein synthesis
Can also act on bacterial ribosomes-> affects commensal microflora in gut
146
How does the shiga toxin move?
Encoded on a bacteriophage
Highly mobile genetic elements and contributes to horizontal gene transfer
Toxins are highly expressed when the lytic cycle of the phage is activated
147
Where can EAEC colonize?
Small and large bowels
Enteroaggregative e. coli
148
What is the important virulence factor in EAEC?
Aggregative adherence fimbriae (AAF)
Genes encoding for AAF are on a plasmid
Mobilized between strains
AAF required for adhesion to enterocytes
AAF stimulate a strong IL-8 response allowing biofilm formation
Along with other virulence factors-> disruption of actin cytoskeleton -> exfoliations
149
What are the important communicable disease in Europe?
Respiratory tract infections
Sexually transmitted infections, including HIV and blood-borne viruses
Food- and waterborne diseases and zoonoses
Emerging and vector-borne diseases
Vaccine-preventable diseases
Antimicrobial resistance and healthcare-associated infections
150
What respiratory tract infections are important in Europe?
Influenza
Animal influenzas, including avian influenza
SARS - Severe acute respiratory syndrome
Legionnaires’ disease (legionellosis)= legionella pneumophila (GN)
Tuberculosis= mycobacterium tuberculosis (GP)
151
What sexually transmitted infections are important in Europe?
```
Chlamydia trachomatis infection (GN)
Gonorrhoea (Neisseria gonorrhoeae) (GN)
Hepatitis B virus infection
Hepatitis C virus infection
HIV/AIDS
Syphilis (Treponema pallidum) (GN)
```
152
What food and waterborne diseases and zoonoses are important in Europe?
Anthrax (GP= Bacillus anthracis -hoofed animals i.e. sheep, cattle, and goats,
but humans who come into contact with infected animals can get sick)
Botulism (GP= Clostridium botulinum- through wounds, canned/preserved food)
Brucellosis (GN= Brucella spp. caused by ingestion of unsterilized milk or meat)
Campylobacteriosis (Campylobacter sp. mostely C. jejuni)
Cholera (GN= Vibrio cholera)
Infection with Vero/shiga toxin-producing Escherichia coli (GN)
Leptospirosis (GN= Leptospira spp.)
Listeriosis (GP= Listeria monocytogenes)
Salmonellosis (GN= Salmonella sp.)
Shigellosis (GN= Shigella sp.)
Tularaemia (GN= Francisella tularensis)
Typhoid/paratyphoid fever (GN= Salmonella typhi and S. Paratyphi)
Yersiniosis (GN= Yersinia enterocolitica)
153
What emerging and vector-borne diseases are important in Europe?
```
Malaria
Plague (Yersinia pestis= GN)
Q fever (Coxiella burnetti= GN)
Severe acute respiratory syndrome (SARS)
Smallpox (A VIRUS, now eradicated)
Viral haemorrhagic fevers (VHF)
West Nile fever
Yellow fever
```
154
What vaccine preventable diseases are important in Europe?
Diphtheria (Clostridium diphtheriae= GP)
Invasive Haemophilus influenzae disease (GN)
Invasive meningococcal disease (Neisseria meningitidis= GN)
Invasive pneumococcal disease (IPD) (Streptococcus pneumoniae= GP)
Measles
Mumps
Pertussis (Bordetella pertussis= GN)
Polio, Rabies, Rubella
Tetanus (Clostridium tetani= GP)
155
What kind of infection is chlamydia?
STI (most frequent in Europe)
Gram negative
Chlamydia trachomatis infection
Obligate IC bacterium (can only grow and divide within host cells)
156
What kind of bacteria is syphilis?
Spirochete
| Gram negative
157
What infection is most common problem of chlamydia?
Adult inclusion conjunctivitis
Results from C trachomatis serotypes D-K, causing chronic follicular conjunctivitis that can occur in adults or in the neonate
158
What is neisseria gonorrhoeae? What are its important virulence factors?
GN diplococcus
Causes infection in urogenital tract but interacting with non-ciliated epithelical cells
Virulence factors:
Pili and antigenic variation-> escape detection and clearance by immune system
159
What is campylobacter sp. (c. jejuni mostly)? What are its important virulence factors?
Most commonly reported infectious GI disease in the EU
Usually sporadic cases
Small children 0-4 years= highest risk group
Infection most likely through undercooked poultry
Virulence factor=
Adhesion and invasion factors, flagella motility, type IV secretion system, toxin
160
What is salmonella sp.? What are its important virulence factors?
One of the most common GI infections in the EU
Undercooked poultry
Outbreaks
Highest infection rate in small children (0-4 years)
Virulence= type III secretion systems encoded on pathogenicity islands (SPI)
Salmonella enterica
Type III secretion system
SPI1: is required for invasion
SPI2: intracellular accumulation
161
What is vibrio cholerae? What are its important virulence factors?
Cholera is an acute, severe diarrheal disease
Without prompt rehydration, death can occur within hours of the onset of symptoms
Virulence=
Type IV fimbria cholera toxin carried on a phages
162
What are listeria monocytogenes? What are its important virulence factors?
Bacteria
Affect risk group= immuno-compromised, elderly, pregnant and their fetus
Listeria can enter non-phagocytic cells and cross three tight barriers (intestinal barrier, BBB and maternofetal barrier)
163
What diseases have we managed to eradicate?
Smallpox
Poliomyelitis
More the 97% decrease in other leading diseases due to mass vaccinations
164
What is an antimicrobial agent?
Interferes with growth and reproduction of a microbe
Used to treat infections
165
What is an antibacterial agent?
Agents to reduce or eliminate harmful bacteria
Type of antimicrobial
For humans or animals
166
When are healthcare-associated infections likely to occur?
More than 48 hours after admission to hospital
167
What are the most frequent types of healthcare-associated infections?
Surgical site infections, urinary tract infections, pneumonia, bloodstream infections and gastrointestinal infections
168
What is the economic cost of hospital acquired infections?
Estimated £1 billion
169
Name three factors
| which can contribute the acquisition of hospital acquired infections
Intervention
Dissemination
Concentration
170
How does intervention contribute to the acquisition of hospital acquired infections?
```
Lines (IV, central, arterial, CVP)
Catheterisation
Intubation
Prostathetic material
Chemotherapy
Prophylactic or inappropriately prescribed antibiotics
```
171
What are the ESKAPE/ESCAPE pathogens?
Enterococcus faecium GP
Staphylococcus aureus GP
Clostridium difficile GP (or Klebsiella pneumoniae GN)
Acinetobacter baumanii GN
Pseudomonas aeruginosa GN
Enterobacter species (inc. e. coli, klesbiella penumoniae, enterobacter species) GN
Resistant to many drugs
Major problem in hospital acquired infections
172
Why is enterococcus faecium a major problem in hospital-acquired infections?
Vancomycin resistance
173
Why is staph aureus a major problem in hospital-acquired infections?
Methicillin resistance (MRSA)
174
Why is clostridium difficile a major problem in hospital-acquired infections?
Can establish infection because of previous antibiotic treatment
175
Why is acinetobacter baumanii a major problem in hospital-acquired infections?
Highly drug resistant
176
Why is pseudomonas aeruginosa a major problem in hospital-acquired infections?
Multi drug resistance i.e. fluoro quinolone-resistant
177
Why is entebacteriaceae a major problem in hospital-acquired infections?
```
Pathogenic E. coli (multi drug resistant)
Klebsiella pneumoniae (multi drug resistant)
Enterobacter species (multi drug resistant)
```
178
Why are clinicians forced to use older, previously discarded drugs e.g. collistin in hospital-acquired infections?
Collistin= associated with significant toxicity
Have to use because poor data to deal with dosages for other disease
179
Why is pathogenic e. coli (a community and hospital acquired infection) problematic?
```
Causes bacteraemia (most common cause by a GN bacteria)
Leads to UTIs
```
Increase in multi-drug resistant strains
Occurrence of resistance to 3rd generation cephalosporins
Many isolates also express the extended spectrum beta lactamase (ESBL)
Still sensitive to carbapenems
180
What are cephalosporins?
Class of beta lactam antibiotics
Inhibit peptidoglycan synthesis pathway by inhibition of activity of penicillin binds proteins (PBPs)
181
What leads to resistance to cephalosporins?
Extended spectrum
β-lactamase (ESBL) encoded on a plasmid
ESBL enzyme cleaves cephalosporin
182
What are carbapenems
Class of beta lactam antibiotics
Inhibit peptidoglycan synthesis pathway byinhibition of activity of penicillin binds proteins (PBPs)
183
What leads to resistance to carbapenems?
Carbapenemase enzyme,
blakpc encoded on a tranposon mobile genetic element
Enzyme cleaves carbapenem
184
What is klebsiella pneumoniae?
Important cause of UTI and respiratory tract infections
Risk group= immuno compromised
High proportion of resistance to 3rd generation cephalosporins, fluroquinolones and aminoglycosides
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is the species of CRE most commonly encountered in the United States
185
What is pseudomonas aeruginosa?
Important cause of infection in immuno-compromised
High proportions of strains are resistant to several antimicrobials (high resistance to carbapenems in Europe)
186
What is MRSA?
Methicillin resistant s. aureus
Most important cause of antimicrobial resistant infection worldwide
187
What is methicillin?
A beta lactam antibiotic
Inhibits peptidoglycan synthesis pathway by inhibition of activity of penicillin binds proteins (PBPs)
188
What causes resistance to methicillin?
Expression of additional
penicillin binding protein
PBP2A has low affinity for methicillin and can still function in the presence of the antibiotic
MRSA strains can synthesis peptidoglycan and survive in the presence of methicillin
189
What is vancomycin resistant enterococcus faecium (VRE)?
Third most frequently identified cause of nosocomial blood stream infections (BSI) identified in the US
Approx 60% resistance to vancomycin
190
What is vancomycin?
Inhibits prostaglandin synthesis by binding to prostaglandin precursor
191
What causes resistance to vancomycin?
Multiple proteins
genes encoded on plasmid or transposon
Results in the synthesis of a different PG precursor
192
True or false: Cephalosporsin is a beta-lactam antibiotic and resistance is due to production of an extended spectrum beta lactamase
True
193
True or false: Methicillin and carbapenem are both beta-lactam antibiotics
True
194
True or false: Carbapenem resistance is frequently found in Klebsiella pneumoniae
True
195
Outline cellular immunity to fungal infection
Opsonization by pentraxin 3 and mannose-binding lectin
Phagocytes= critical first line of defence
NK cells provide early interferon-gamma
If innate immunity fails-> adaptive responses
Dendritic cells influence T cell differentiation Th1 and Th17 play a role
196
What are the types of fungi from Candida albicans (parent yeast cell)?
Budding yeast
Pseudohypha
Germ-tube (can go to pseudohypha and hypha)
197
Give examples of opportunistic fungi and outline how they work
Candida albicans (dimorphism yeast or hyphal forms allows tissue invasion)
Cryptococcus neoformans (forms a capsule to evade phagocytosis)
Aspergillus umigatus (inhaled as conidia, invade as hyphae)
198
How do drosophila have fungal immunity?
Requires toll
199
Why is transplantation associated with risk of fungal infections?
Toll Like Receptor SNPs analysed in 336 haematopoetic stem cell transplant patients and their donors
Risk of aspergillosis assessed by multivariate Cox regression analysis
Associations independently validated in further 103 patients
200
What mutations increase susceptibility to fungal disease?
Mutations in Dectin-1, TLR4 and plasminogen
201
What are PAMPs associated with?
Pattern recognition receptors implicated in fungal immunity
Pattern recognition receptors (PRRs) play a key role in the innate immune response by recognizing conserved pathogen associated molecular patterns (PAMPs)
202
What immune cells contribute to fungal immunity?
Marcophages and neutrophils
Dendritic cells modulate adaptive immune responses
Adaptive T cell interferon-gamma responses augment host immunity to fungi
Interferon-gamma or adoptive T cell therapy have emerging utility for the treatment of fungal infections
(Neutrophils are especially important in aspergillus)
203
How can gene therapy be used to treat fungal infections?
For primary immunodeficiencies
204
Where are fungal spores commonly found?
Found in the air
| Easily drawn into lungs (e.g. aspergillus spore head)
205
Describe the damage response framework of microbial pathogenesis?
```
Commensal bacteria
Colonization
Latency
Disease
Death
```
206
What kinds of host responses are there?
Normal
Ineffective
Exaggerated
Leads to allergic or invasive fungal disease
207
What is the primary driver of fungal infection?
Aspergillus
Other fungi may also contribute
208
What type of hypersensitivity reactions are there to fungal infections?
Type 1/111/IV hypersensitivity reactions
209
What are the criteria for allergic bronchopulmonary aspergillus?
Predisposing conditions= asthma or cystic fibrosis
Obligatory criteria
- Total baseline serum IgE >1000 IU/ml
- Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
Supportive criteria (more than 2 present)
- Eosinophilia >500cells/ul
- Serum precipitating or IgG antibodies to Aspergillus fumigatus
- Consistent radiographic abnormalities
210
What are the radiological features of ABPA?
Dilated bronchi with thick walls
Ring or linear opacities
Upper or central region predeliction
Proximal bronchiectasis
Lobar collapse due to mucous impaction
Fibrotic scarring
211
How do you manage ABPA?
Corticosteroids
Itraconazole for steroid sparing effect
Benefit of itraconazole past 16 weeks unclear
Reduction in circulating IgE, steroid dependency and improved PFT
Itraconazole indicated if not responding to steroids or steroid- dependent
Role of inhaled steroids and other antifungals less clear
Recombinant IgE monoclonal antibodies (omalizumab) may be useful
212
What pulmonary allergy to fungi is best recognised?
Allergic bronchopulmonary aspergillosis
213
What is the evidence for fungal sensitisation?
Hypersensitivity pneumonitis
214
How do you diagnose ABPA?
Diagnosis driven by skin test, IgE and IgM in clinical relevant populations
215
Define: infection
Invasion by and growth of
pathogenic microorganisms
within the body
216
Define: disease
A disordered or incorrectly functioning organ, part, structure or system of the body
Results from the effect of genetic or developmental errors, infection, poisons, nutritional deficiency or imbalance, toxicity or unfavorable environmental factors, illness, sickness, ailment
217
What is a parasite?
Organism living in or on the host and dependent on it for nutrition- causing damage
218
Give examples of endoparasites
Protozoa= amoeba, coccidian, ciliate, flagellates
Metazoa= roundworms, flatworms, flukes
219
What are Protozoa?
Single celled organisms (unicellular eukaryotes) with a nucleus and complex organelles in cytoplasm
Type of endoparasites
E.g. amoeba, coccidian, cilia and flagellates
Pathogenesis varied
Some have insect vectors (e.g. malaria)
No eosinophilia
220
What are metazoa?
Multicellular organisms
Free living, intermediate hosts and vectors
Some inhabit gut (e.g. geohelminths) and others invade tissues (e.g. eosinophilia if they invade blood)
E.g. helminths, roundworms, flatworms, flukes
221
Give examples of protozoa
Amoebae: Entamoeba histolytica, Entamoeba dispar
Coccidia: Plasmodium species, Toxoplasma, Cryptosporidium
Ciliates: Balantidium coli
Flagellates: Trichomonas, Giardia, Trypanosoma, Leishmania
222
How does infection by protozoan amoebae occur?
Ingestion of mature cysts in food or water
Or on hands contaminated by faeces
Humans are the only reservoir
223
Outline the epidemiology of entamoeba histolytica
10% of world's population is infected
Causes death of parasitic infections
Common in S & C America, W & SE Asia
90% infections are asymptomatic
10%-> dysentry to amoebic liver abscess
Incubation period may be 7 days
Tissue invasion happens in first 4 months
224
Outline the e. histolytic life cycle
Encystation
Immature cyst
Quadrinucleate cyst
Noninvasive infection (cysts exit host in the stool)
Ingestion in contaminated food and water
Mature cyst
Excystation
Trophozoites migrate to the LI
Trophozoites multiply by binary fission
THEN EITHER BACK TO ENCYSTATION OR TOWARDS INVASIVE INFECTION
Trophozoites invade the intestinal mucosa
Invasive infection
225
How does e. histolytic (amoeba) spread?
Cysts enter the small intestine and release active amoebic parasites (trophozoites) which invade the epithelial cells of the LI
Leads to flask-shaped ulcers
Infection can spread from intestines to other organs e.g. liver, lungs and brain via the venous system
226
How long can cysts of e. histolytic survive?
Asymptomatic carriers pass cysts in the faeces and the asymptomatic carriage state can persist indefinitely
Cysts remain viable for up to 2 months
227
What does invasive amoebiasis cause?
An amoebic liver abscess
May affect the lung, heart, brain, urinary tract and skin
228
What is the difference between e. histolytica and e. dispar?
E. histolytica= the cause of invasive amoebiasis
E. dispar= normal commensal of the GI tract
229
How is amoebiasis diagnosed?
Laboratory
Bright-field microscopy= e. histolytica and e. dispar morphologically identical species
Usually spherical
Immature cyst have 1-3 visible nuclei
Mature cyst has 4 nuclei
230
How is amoebiasis treated?
Nitroimidazole derivatives (act on trophozoite, but not on cysts) and parmomycine or diloxanide furoate
231
What are coccidian infections in humans usually?
Zoonoses
| NB. They are endoparasites- protozoa
232
Give examples of coccidia and what they cause
Plasmodium species from mosquitos -> malaria
Toxoplasma from cats and kittens -> toxoplasmosis
Cryptosporidium from water -> diarrhoea
233
What is toxoplasmosis?
Caused by toxoplasma (a type of coccidia)
Mild disease in immunocompetent individuals, fever, swollen lymph nodes, headaches, sore throat
However, in pregnancy= serious danger for the foetus
234
What is diarrhoea?
Mild disease in immunocompetent individuals, the parasites can cause serious pathological changes in immunocompromised individuals
235
What are the hosts of malaria and the stages?
2 types of host: humans and female anopheles mosquitoes
2 stages in human: liver and blood stages
236
What are the symptoms of malaria?
Fever, headache, chills, vomiting, muscle pain
Paroxysm (cycle in 4-8hrs)
```
Complications of malaria:
Severe anemia (destruction of red cells)
Cerebral malaria (swelling of the brain, seizures, coma)
```
```
Liver failure
Shock
Pulmonary oedema
Abnormally low blood sugar
Kidney failure
Swelling and rupturing of the spleen
```
237
What are the treatments of malaria?
UNCOMPLICATED MALARIA
chloroquine, Atovaquone-proguanil, Artemether-lumefantrine, quinine sulfate
Plus one of the following: Doxycycline, Tetracycline or Clindamycin Quinine sulfate, Mefloquine
SEVERE MALARIA
Artemisinin-based combination therapy (ACT) is recommended for the treatment of P. falciparum malaria
238
How is malaria diagnosed?
Blood film, giemsa stained
Rapid test= commercially available antigen detection tests (more expensive and less sensitive)
239
How do humans become infected by toxoplasma gondii?
Humans can become infected by any of several routes:
Eating undercooked meat of animals harboring tissue cysts
Consuming food or water contaminated with cat feces
By contaminated environmental samples
Blood transfusion
Organ transplantation
Transplacentally from mother
to fetus
240
What happens to immunocompromised patients infected with toxoplasma?
May develop CNS disease, brain lesions, pneumonitis or retinochoroiditis
241
What does cryptosporidium cause?
Cryptosporidiosis
Causes diarrhea, fever, nausea, vomiting in humans
Very common in HIV+ patients presenting with diarrhoea
242
How is cryptosporidosis diagnosed?
Stool examination
243
How is cryptosporidosis treated?
Fluid rehydration
244
What are the ciliates (endoparasites- protozoa)?
E.g. Balantidium coli (balantidiasis)
Reservoir hosts= pigs, rodents, primates
Worldwide distribution
245
What happens when people are infected with balantidium coli (balantidiasis)?
Most people infected-> no symptoms
Immunocompromised patients-> persistent diarrhea, dysentery, abdominal pain, weight loss, nausea and vomiting
If left untreated, perforation of the colon can occur
246
How is balantidium coli diagnosed?
Stool examination
247
What is giardiasis?
Commonest, globally distributed, water-borne protozoal infection
Flagellated trophozooites attach by their suckers to surface of the
duodenal or jejunal mucosa
Ovoid cysts are able to survive standard chlorination procedures,
filtration is required to exclude them from drinking water
Causes diarrhoea
248
What are the symptoms of giardiasis?
```
Diarrhoea
Greasy stools that tend to float
Stomach or abdominal cramps
Upset stomach or nausea and vomiting
Dehydration (loss of fluids)
```
249
How is giardiasis diagnosed?
Stool examination (look at cysts and trophozoites)
250
How is giardiasis treated?
Metronidazole
| Tinidazole
251
How are trichomonas transmitted?
Sexually
252
Where is trichomoniasis infection found?
Women= vagina, urethra and paraurethral glands
Men= urethra
253
What are the symptoms of trichomoniasis?
FEMALES
10-50% are asymptomatic
Vaginal discharge, vulval itching, dysuria or offensive odour
Occasionally the presenting complaint is of low abdominal discomfort or vulval ulceration
MALES
15 to 50% of men are asymptomatic
Discharge or dysuria
Complications
Detrimental outcome on pregnancy and is associated with preterm delivery and low birth weight
254
What happens with HIV and trichomoniasis?
Growing evidence that trichomonas infection may enhance HIV transmission
There may be an increased risk of TV infection in those that are HIV positive
255
How is trichomoniasis diagnosed?
Microscopy (detect motile trichomonads in swab and urine)
| Trichomonas rapid test
256
How is trichomoniasis treated?
Metronidazole
257
What kind of disease is leishmania?
Flagellate (endoparasites- protozoa)
258
What are helminths (metazoa)?
Complex muticellular parasites
Cycles may involve insect vectors and intermediate hosts
Humans normally the host (few are zoonoses)
Adult worms cannot multiply in man
Lay eggs, microfilaria, larvae
259
Give examples of helminth infections
Ascariasis
Trichuriasis
Hookworm infection
Schistosomiasis
260
Give examples of helminth worms
Roundworms (nematodes)= ascaris, hookworm, filaria, strongyloides
Flatworms (cestodes)= taenia (tapeworms)
Flukes (trematodes)= schistosoma
261
What do ascariasis infections cause?
Large bolus of roundworms (can be expelled after antihelminthic treatment)
262
What happens in ascariasis?
Adult worms live in the lumen of the SI
After infective eggs are swallowed, the larvae hatch, invade the intestinal mucosa and are carried to the lungs (via portal then systemic circulation)
Larvae mature further in lungs-> penetrate alveolar walls-> ascend bronchial tree to the throat-> swallowed
Reach SI and develop into adult worms (can live 1-2 years)
263
What are the symptoms of ascariasis?
No symptoms in some
Adults feed on the contents of the
small intestine and in heavy infections, this may
compound problems in malnourished individuals
Migration of large may cause localised reactions in various organs
Lung penetration can cause Loeffer's pneumonia (resulting bacterial infections can be fatal)
264
How is ascariasis diagnosed?
Stool examination
265
How is ascariasis treated?
Albendazole
| Mebendazole
266
What is ancylostoma duodenale?
Roundworm
Parasitic nematode worm
Hookworms
About 1cm long and curved
They are attached by their
buccal capsules to the villi
of the small intestine
267
How are people infected with a hookworm?
Larvae carried through blood vessels to the heart and then to the lungs
Penetrate into the pulmonary alveoli, ascend the bronchial tree to the pharynx and are swallowed
Larvae reach SI and mature into adults
Attach to intestinal wall with resultant blood loss by the host
268
What are the symptoms of hookworms?
Iron deficiency anaemia (caused by blood loss at site of intestinal attachment of adult worms)
Cardiac complications
GI and nutrition or metabolic symtpoms
Local skin manifestations
Respiratory symtoms can be observed during pulmonary migration of the larvae
269
How are hookworms diagnosed?
Stool examination
270
How are hookworms treated?
Albendazole
| Mebendazole
271
What causes whipworm?
Eggs hatch in the SI
Release larvae that mature and establish themselves as adults in the colon
Adult worms live in cecum and ascending colon
Adult worms are fixed in the location
272
What are the symptoms of whipworm?
Some have no symptoms
Hundreds of worms cause symptoms:
Blood diarrhoea and anaemia (severe vitamin and iron loss)
Worms leave open wounds which cause inflammation of the intestinal wall
Some cases-> rectal prolapse
273
How do you diagnose whipworms?
Stool examination
274
How are whipworms treated?
Albendazole
| Mebendazole
275
What is helminthic therapy?
Whipworm is one of the worms being used in helminthic therapy which helps against allergies and autoimmune diseases
276
Give examples of diseases caused by lymphatic filariasis
Elephantiasis
Wucheria bancrofti
Brugi malayi
277
How is lymphatic filariasis diagnosed?
During the day, they are present in the deep veins, and during the night, they migrate to the peripheral circulation
Blood smear or antigen detection with a immunochromatic test (card) or ELISA
278
How is lymphatic filariasis treated?
Albendazole
| Ivermectin
279
What does loaiasis cause?
Loa loa
| Eye worm
280
What is loaiasis?
Confined to Africa
Adult worms live in man for 4-12 years
Females migrate through the subcutaneous tissues, may cross the front of the eye under the conjunctiva
Microfilariae develop from larvae in the female and circulate in the blood from where they may be picked up by chrysops and in the gut of the fly, the microfilariae enter the fat bodies and mature into infective third stage larvae
Larvae infect a new host when Chrysops takes a bloodmeal and mature into adult worms within about one year
281
What are the hosts for tapeworms?
Taenia solium and taenia asiatica= pig
| Taenia saginata= beef
282
What are the symptoms of taenia?
Most people have no symptoms
T. saginata taeniasis -> more symptoms
Can cause digestive problems including weight loss and upset stomach
Active passing of tapeworm segments
283
How is taenia diagnosed?
Segment in stool or identification of eggs in stool
284
How is taenia treated?
Praziquantel
285
What is the commonest cause of acquired epilepsy?
Taenia solium- cysticercosis
286
How does schistosomiasis infect humans?
Snails
Eggs eliminated in water via faeces or urine
Hatch and release miricidia
Penetrate the sail
Release as cercariae
Penetrate the slin
Will migrate through different tissues and transform into adult male and female worm and will eventually reside in venules
Eggs are moved progressively towards the lumen of the intestine and bladder and ureters
287
What are the symptoms of schistomiasis?
Within days= rash or itchy skin
Within 1-2 months= fever, chills, cough, and muscle aches
When adult worms are present= eggs that are produced usually travel to the intestine, liver or bladder, causing inflammation or scarring
Children who are repeatedly infected can develop anaemia, malnutrition and learning difficulties
After years of infection-> the parasite can also damage the liver, intestine, lungs and bladder
288
How is schistomiasis diagnosed?
Stool or urine samples
289
How is schistomiasis treated?
Praziquantel
290
Give examples of ectoparasites
Sarcoptes scabiei (scabies)
Pediculus humanus capitis (head louse)
Pediculus humanus corporis (body louse, clothes louse)
Pthirus pubis ("crab" louse, pubic louse)
291
How is scabies diagnosed?
Appearance of rash and presence of burrows
292
How is scabies treated?
Scabicides
293
What are the stages of ectoparasites?
Eggs, nymphs and adult
294
How are ectoparasites transmitted?
By direct contact
295
Outline the life cycle of Leishmania parasites?
```
Release from macrophages
multiplication
Transformation
Inoculation
Attachment and phagocytosis
Transformation
Multiplication and reinfection
Ingestion
```
SANDFLY THEN VERTEBRATE HOST
296
What are the forms of Leishmania?
promastigote
| Amastigote
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What is promastigote?
Type of leishmania within sand fly vector
Move in the direction of their flagellum
Can be cultured
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What is amastigote?
Type of leishmania within human or other vertebrate host's cells (have resorbed their flagellum)
No longer motile
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Where are sand flies mainly found?
In the warm parts of the world
Including southern Europe, Asia, Africa, Australia, Central and South America
Spreading because of climate change
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What do sand flies look like? How do they act?
Small (3mm)
Hairy
They hop around before settling down to bite
Unlike mosquitoes, their attack is silent
Female, not male, feed on blood which provide nutrition for their eggs
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What are the major forms of leishmaniasis?
Visceral leishmaniasis (Kala azar)
Cutaneous leishmaniasis
Diffuse cutaneous leishmaniasiss
Mucocutaneous leishmaniasis
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What is visceral leishmaniasis? Risk factors?
Affects internal organs
Also called Kala azar (= black fever)
Causes fever, weight loss and enlargement of spleen and liver
FATAL if untreated
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Risk factors for development of clinical
disease include:
Malnutrition
Immune suppressive drugs
HIV co-infections
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How is visceral leishmaniasis diagnosed?
Parasite detection by microscopic examination of aspirates from lymph nodes, bone marrow or spleen aspiration
Antibody detection by direct agglutination test and rK39 chromatographic test
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How is visceral leishmaniasis treated?
FIRST LINE
Sodium stibogluconate (SSG) or Meglumin antimoniate (monotherapy)
Liposomal Amphotericin B (LAmB, AmBisome)
SECOND LINE
Liposomal Amphotericin B
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What is post Kala-azar dermal leishmaniasis (PKDL)?
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Frequent in Sudan and India
Occurs during or after treatment, after sub-clinical infection
Lesions start on face, usually around
mouth
Lesions can become nodular
PKDL can spread to the trunk and limbs
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What are the symptoms of localised cutaneous leishmaniasis?
Crusted or large and irregular ulcers
| Multiple crusted lesions
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What happens in diffuse cutaneous leishmaniasis?
Disseminated infection
Multiple, nodular non-ulcerating lesions
No spontaneous healing-> relapses
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What is cutaneous leishmaniasis?
Skin lesions on exposed body parts, often self-healing
Can create serious disability and scars
Immunity to reinfection
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What is diffuse cutaneous leishmaniasis?
Disseminated lesions
Resembles leprosy
Difficult to treat, no spontaneous healing, frequent relapses
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What is mucocutaneous leishmaniasis?
Disfiguring
| Destroys mucous membranes
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How is HIV infection related to leishmaniasis?
HIV infection can lead to reactivation of latent Leishmania infection or to symptomatic VL at initial
infection
