Microbiology Flashcards
(230 cards)
1
Q
Which 3 fungi are most likely to pose a threat/be able to infect humans?
A
- Candida species
- Aspergillus
- Cryptococcus species
2
Q
What patients are at particular risk to fungal infections?
A
o immunocompromised due to fungi mauinly being opportunistic pathogens
- HIV patients are more likely to suffer from cryptococcus infections due to a lack of CD4 cells -> fungal meningitis
- pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is associated with AIDS
o high risk patients have prolonged and profound neutropenia after treatment with highly cytotoxic chemotherapy for haematological malignancies and recipients of haematopoietic stem cell transplantation (HSCT)
3
Q
How are dendritic cells and fungal infections linked?
A
- dendritic cells have an instrumental role in linking innate and adaptive responses to a range of pathogenic fungi
- signals transmitted by dendritic cells activated by exposure to fungi vary depending on the encountered fungus and its morphotype, helping to shape the appropriate adaptive immune response
4
Q
What is the predominate protective mechanism to fungal infection?
A
- Th1 type CD4+ T cells
5
Q
What cytokine is important in the Th1 type CD4+ T cell response to fungi?
A
- interferon-γ
6
Q
Summarise cellular immunity to fungal infection.
A
- opsonisation by pentraxin 3 and mannose-binding lectin
- phagocytes are a critical first line of defence -> NK cells provide early interferon-gamma
- failure of innate immunity leads to adaptive responses -> dendritic cells influence T cell differentiation (Th1 and Th17 play a role)
o INNATE IMMUNITY IS MORE IMPORTANT THAT ADAPTIVE in fungal infection rather than the adaptive immunity -> loss of neutrophils is a big risk factor for infection
7
Q
Where are most fungal infections found?
A
o mucosal surfaces
- mould (contains multicellular filaments) = lungs -> candida and aspergillus
- yeasts (single cells) = gut -> cryptococcus -> forms a capsule to evade phagocytosis
8
Q
What receptors are important in sensing fungal components?
A
- toll like receptors
9
Q
Name some human susceptibilities to fungi.
A
- human dectin-1 deficiency
- human CARD9 deficiency
- TLR4 mutations/polymorphisms
- some plasminogen alleles
10
Q
How does human dectin-1 deficiency increase the risk of fungal infection?
A
- human dectin-1 is important in the phagocytosis of candida -> HD1 is important for immunity to chronic mucocutaneous candidiasis -> very unpleasant disease that leads to massive hypertrophy of the mucosa and many problems with fungal drug resistance
- loss of function in HD1 -> Mendelian susceptibility to chronic mucocutaneous candidiasis -> patients with the homozygous mutation have a reduced inflammatory response via IL-6
11
Q
How does human CARD9 deficiency increase the risk of fungal infections?
A
- human CARD9 deficiency causes chronic mucocutaneous candidiasis
- CARD9 is an adaptor molecule downstream of the C-type lectins
- suffers are susceptible to mucosal and invasive infection (including CNS fungal disease)
- functional CARD9 is required for TNF-alpha production in response to beta-glucan stimulation and T cell Th17 differentiation in humans -> if deficient they can’t respond to fungi
12
Q
When are patients with TLR4 mutations/polymorphism particularly vunerable to fungal infection?
A
- stem cell transplant patients -> are at high risk of candida and aspergillosis due to reduce immune system
13
Q
Which white blood cell is the most important in the defence against fungi?
A
- neutrophils
14
Q
Describe neutrophil nets.
A
- neutrophils can form neutrophil nets -> are extracellular fibres mainly comprised of DNA from the neutrophils which can bind to extracellulr pathogens and prevent them from replicating -> reduces damage to host cells
- the net is sticky -> reason for sputum being sticky during chest infection
- deficiency to create these increases infection risk
15
Q
What is chronic granulomatous disease?
A
- sufferers have a loss of gp91 function (mutation) due to a defects in the enzyme NADPH oxidase -> NADPH oxidase is important for the generation of reactive oxidative species -> their neutrophils are unable to kill ingested pathogens
- patients are susceptible to invasive fungal infections, particularly with Aspergillus species
- confirms the crucial role of neutrophils in defence against fungal infections
16
Q
What treatments are available for ghronic granulomatous disease?
A
- gene therapy can allow some restoration of function of the gp91 (FOX91)
17
Q
What do many fungal spores cause?
A
- allergic disease -> rhinitis, dermatitis, asthma and ABPA
- spores can easily disperse and enter teh lungs hence the reasoning for them causing lung problems
18
Q
What is ABPA?
A
- allergic broncho-pulmonary aspergillosis
- is a condition associated with asthma
- involves an allergy to aspergillus and destruction of the airways -> bronchiectasis -> airway gets wider -> more prone to infections
19
Q
What is the criteria for ABPA?
A
o patient has a predisposing condition -> asthma or cystic fibrosis
o obligatory criteria -> total baseline serum IgE > 1000 IU/ml and a positive immediate hypersensitivity skin test or Aspergillus-specific IgE
o 2 or more of the supportive criteria:
- eosinophilia > 500 cells/ul
- serum precipitating or IgG antibodies to aspergillus fumigatus
- consistent radiographic abnormalities -> dilated bronchi with thick walls, ring or linear opacities, upper or central region predilection, proximal bronchiectasis, lobar collapse due to mucous impaction, fibrotic scarring
20
Q
How is ABPA managed?
A
- corticosteroids and itraconazole for steroid sparing effect
21
Q
What is hypersensitivity pneumonitis?
A
- an allergic response requiring long-term allergen exposure (as a consequence, often occupational)
- cell-mediated delayed sensitivity reaction and allergen-specific precipitins usually present
22
Q
What is the role of the IRF-7 gene?
A
o a key player in the interferon induction pathway
- can inherit two copies of a faulty IRF-7 gene -> gene product doesn’t work very well -> people therefore cannot produce interferon alpha in response to infection
23
Q
What is the role of IFNAR2 gene?
A
o an interferon alpha receptor
- if you inherit 2 recessive defective/mutated IFNAR2 genes -> often due to deletion out of frame leading to a premature stop codon
- can’t respond to interferons produced in an infection
24
Q
What should not be given to patients with autonomal recessive IFNAR2 gene mutated patients?
A
- live attenuated vaccines -> virus can manifest in the body and can kill these patients
25
What is the role of the IRF-3 gene?
- part of the interferon signalling pathway
- patients suffering from heterozygous mutations in this gene don't respond well to viruses as they cannot produce interferon responses
26
What are interferons?
- a soluble protein factor that binds to receptors adn signals the activation of de novo transcritption of 100s of interferon stimulated genes (ISGs) that produce an anti-vrial state in cells -\> cells can't be infected by a virus
27
Why are interferons not used as a anti-viral, especially for illness such as the common cold?
- have many side effects -\> all the aches, pain and fever that you have when ill with a virus
- taking interferons for most viral infections would make you feel more ill than you originally did
28
What are the 3 major functions of type I interferons?
- induce an anti-microbial state in both the infected and neighbouring cells
- modulate the innate response to promote Ag presentation and NK but inhibit pro-inflammation
- activate the adaptive immune response
29
What cell types produce type I interferons and what are their consequences?
- IFN-alpha = plasmacytoid dendritic cells -\> recruits APCs and adaptive immune cells
- IFN-beta = all cells -\> diffuse and interacts with neighbouring cells -\> leads to switching on of ISGs in those cells too
30
Describe type II IFN.
- type II IFN is IFN-gamma which is a highly specialised immune signalling molecule produced by immune cells activated by T and NK cells
- signals through the IFN-gamma receptor
31
Describe type III IFN.
- type III INF is IFN-lambda
- thought to protect barriers of your body from viral infection -\> present mainly on epithelial surfaces as a consequence -\> especially found on the respiratory tract and liver
- signal through IL28 and IL10-beta receptors
32
How do we differentiate between self and non-self in the case of viruses?
- a virus cannot hide its nuclei acid
o PAMPS (pathogen associated molecular patterns) are unique to pathogens -\> often foreign nucleic acid
o PAMPS are recognised by PRPs (pattern recognition receptors)
- PRPS can be RLRs (cytoplasmic RIG-I like receptors) or TLRs (endosomal Toll like receptors)
o cytoplasmic nucleotide oligomerisation domain receptors (NLRs) also exist
33
Describe interferon induction.
- PRRs (e.g. RIG-I like receptors) detect PAMPs such as single stranded RNA in the cytoplasm of the cell
- RIG-I will then signal through Mavs (located on the mitochondrion)
- this triggers signalling through various different pathways that result in the translocation of molecules from the cytoplasm to the nucleus
- transcription factors will become phosphorylated, they will bind to the promoter regions of target genes (in this case IFN beta). It will generate IFN beta transcripts
- IFN beta is then released from these cells and travels to neighbouring cells to induce an anti-viral state -\> way we/the host controls the amount of virus in the body
34
How do TLRs and cytoplasmic sensors detect viral infection?
- TLRs can sense the nucleic acids in the endosome and it will signal to a molecule outside the endosome (MyD88) -\> sends various transcription factors to the nucleus of the cell -\> results in the switching on of expression of IFN-alpha
35
How are DNA viruses detected?
- in a normal, healthy cell, ALL the DNA should be in the nucleus
- DNa in the cytoplasma is detected by cGAS (an enzyme) whichs binds the DNA, and synthesises another small molecule (cGAMP), which binds to a STING molecule
- STING uses the same pathway as IRF-3 -\> moves into the nucleus to transcribe some new IFN molecules
36
How do IFN contain viruses to a small area?
- IFN binds to the IFN receptor on neighbouring cell (present on every cell in the body) -\> this activates the Jak and Tyk pathway
- then goes on to phosphorylate the STAT molecules -\> STAT molecules dimerise and combine with IRF9 -\> then goes to the nucleus and binds to a promoter region that is responsive to that TF -\> cell becomes a very hostile place for a virus so it can't move
37
Name some interferon stimulated genes.
- PKR Protein Kinase R -\> inhibits translation
- 2’5’OAS -\> activates RNAse L that destroys single stranded RNA including mRNA
- Mx -\> inhibits incoming viral genomes -\> wraps around viruses to prevent cell entry
- ADAR -\> induces errors during viral replication (attacks the virus as it’s replicating)
- IFITM3 -\> restricts virus entry through endosomes
- serpine -\> activates proteases which digest viral proteins
- viperin -\> inhibits viral budding
38
WHat viruses are prevented from replicating by Mx genes?
- Mx1 = influenza, rabdoviruses -\> traps the viral DNA as they release their nucleic acid
- Mx2 = HIV -\> upregulation of Mx2 prevents HIV from injecting its RNA genome into cell nucleus
39
How long do an anti-viral state triggered by interferons last in cells?
- IFN response may only be maintained for several hours (maybe a day) -\> subsequently the ability to response to IFN is lost due to negative regulation
- negative feedback controls to turn off the IFN response as well as SOCS (suppressor of cytokine signalling) genes that turn off the response
40
How have viruses evolved to evade IFN responses?
- avoid detection by hiding the PAMP -\> some create a membrane which they replicate within
- 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
41
How does hepatitis C virus prevent IFN control?
- produces NS3/4 protease which acts as an antagonist to interferon induction by cleaving MAVS
42
How does influenza virus prevent IFN control?
- produces NS1 protein which acts as antagonist to interferon induction by binding to RIG-I /TRIM25/RNA complex and preventing activation of signalling pathway and also prevents nuclear processing of newly induced genes
43
How do Pox viruses prevent IFN signals?
- pox viruses (and herpes) viruses are large DNA viruses -\> over half the pox virus genome is comprised of accessory genes that modify immune response
- pox viruses encode soluble cytokine receptors (vaccinia virus B18), which mop up IFN -\> IFN cannot interact with receptor
44
What is the potential clinical use for viruse endoced soluble cytokine receptors such as vaccinia virus B18?
- being developed as possible immune therapies for autoimmune and inflammatory conditions in which IFN and other cytokines are produced in abundance and contribute to the pathology of the condition
- e.g. rheumatoid arthritis
45
How does ebola virus evade the immune mechanisms?
- RIG-I and Mda-5 sense the ebola virus
- VP35 is a protein produced by ebola that BLOCKS the signalling cascade
- VP24 is another protein produced by ebola that blocks the signal from the IFN receptor into the nucleus -\> no ISGs can be transcribed
46
How can viruses produce cytokine storms?
- virus replicates and induces high levels of IFN accompanied by massive release of TNF alpha and other cytokines -\> differences in outcome may reflect vigour of the innate immune system, which varies with age
- typical of dengue haemorrhagic fever, severe influenza infections and ebola
47
What are the consequences of cytokine storms?
- cytokine storm will lead to pulmonary fibrosis, which is caused by the accumulation of immune cells in the lung spaces
- eventually the patient will succumb to the immune pathology rather than from damage from the virus
- young, healthy people infected by these viruses have a worse prognosis because they have vigorous immune system which will produce a strong response
48
What kind of viruses could be used as a new generation of live attenuated vaccines?
- viruses deficient in control of IFN are attenuated in IFN competent cells -\> means that they induce high levels of interferon when they enter these cells
- high IFN levels they induce can also recruit useful immune cells, IFN acting as an ‘adjuvant’ -\> IFN levels strongly switch on the antiviral response
49
How could viruses be used as a cancer treatment?
- cancer cells don’t make a very good IFN response could lead us to the generation of rationally designed oncolytic viruses
- giving a cancer patients a virus defective to fight the IFN response throughout the body -\> therefore only replicates in and kills the cancer cells. and all the healthy cells in a person’s body (have a perfectly good IFN) will not be killed
50
Name some common virulence factors associated with bacterial infections.
- diverse secretion systems -\> allows them to get proteins from the cytoplasm of the cells into host cells
- flagella
- pili -\> important adherence factors
- capsule -\> protects against phagocytosis -\> i.e. Streptococcus pneumoniae
- endospores -\> metabolically dormant forms of bacteria -\> I.e. Bacillus sp. and Clostridium sp.
- biofilms -\> organized aggregates of bacteria embedded in polysaccharide matrix which can lead to antibiotic resistant -\> i.e. Pseudomonas aeruginosa and Staphylococcus epidermidis
- exotoxins and endotoxins
51
Describe the different types of exotoxins.
- neurotoxins -\> act on nerves or motor endplate -\> i.e. Tetanus or Botulinum toxins
- enterotoxins -\> act on the GI tract -\> infectious diarrhea i.e. Vibrio cholera, Escherichia coli, Shigella dysenteriae and Campylobacter or food poisoning i.e. Bacillus cereus or Staphylcoccus aureus
- pyrogenic exotoxins -\> stimulate release of cytokines -\> i.e. Staphylcoccus aureus or Streptococcus pyogenes
- tissue invasive exotoxin -\> allow bacteria to destroy and tunnel through tissue -\>
i. e. Staphylococcus aureus, Streptococcus pyogenes, Clostridium perfringens
- miscellaneous exotoxin -\> specific to a certain bacterium and/or function not well understood -\> i.e. Bacillus anthracis and Corynebacterium diphtheriae
52
Describe endotoxins.
- endotoxins are only produced by gram-negative bacteria
- are a lipid A moiety of the lipopolysaccharide layer -\> are shed in steady amounts from living bacteria
- due to endotoxins treating a patient who has a gram-negative infection with antibiotics can sometimes worsen condition because when bacteria lyse they release large quantities of LPS/endotoxin -\> septic shock
53
Define outbreak.
- 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
54
How can outbreaks be identified?
- surveillance -\> provides an opportunity to identify outbreaks
- good and timely reporting systems are instrumental in idenitifcation
55
What is haemoltyic-uremic syndrome?
- characterised by a triad of acute renal failure, hemolytic anemia and thrombocytopenia
- usually found in children -\> very rare in adults
- caused by the Shiga toxin producing E. coli strain O157:H7
- reservoir are normally ruminants – mostly cattle
- human infection occurs through the inadvertent ingestion of fecal matter and secondary through contact with infected humans
56
How does Shiga/vero toxin function?
- StxA (a subunit found in SHiga toxin family members) is an enzyme that cleaves the 28S ribosomal RNA in eukaryotic cells -\> inhibition of protein synthesis -\> decreased proliferation of susceptible bacteria -\> can affect commensal gut microflora
- Shiga toxin does not only block protein synthesis in eukaryotic cells but also affects several other cellular processes
57
Can Shiga toxins move from bacteria to bacteria?
o yes
- Shiga toxins are encoded on a bacteriophage -\> can be transferred from one strain to another via a phage
- phage particles enter the environment, and infect a closely related strain to produce the toxin
- highly mobile genetic elements and contributes to horizontal gene transfer
- toxins are highly expressed when the lytic cycle of the phage is activated
58
Where can E. coli strains colonize?
- EHEC = large bowel
- EAEC = both small and large bowel
59
What are the 6 categories of communicable disease in Europe?
1. respiratory tract infections
2. sexually transmitted infections, blood-borne viruses
3. food and waterborne diseases and zoonoses
4. emerging and vector-borne diseases
5. vaccine-preventable diseases
6. anti-microbial resistance and healthcare-associated infections
60
What respiratory tract infections must be reported in Europe?
- influenza - viral
- animal influenzas -\> including avian and swine - viral
- SARS (severe acute respiratory syndrome) - viral
- Legionnaires’ disease -\> Legionella pneumophila - gram -ve bacteria
- tuberculosis -\> Mycobacterium tuberculosis - gram +ve bacteria
61
Where is Leigonella pneumophila found?
- gram negative bacterium is found in amoeba in ponds, lakes and air conditioning units
62
What is Leigonella pneumophila route of infection to humans?
- inhalation of contaminated aerosols -\> will infect and grow in alveolar macrophages
- human infection is “dead end” for the bacteria/bacteria can’t survive here on
63
Describe the importanr virullent factor of Legionella pneumophila.
o type IV secretion system
- allows L. pneumophila to infect and replicate in human macrophages by allowing the bacterium to secrete from inside to the outside
- macrophages take up these bacteria in humans and are able to replicate in macrophage vacuoles, because it can release special virulence factors (due to the type IV secretion system)
64
Describe mycobacterium tuberculosis.
- grouped as a gram-positive bacteria, but it has a very different cell wall -\> has an extra lipid layer which makes treatment more difficult as drugs cannot access the bacteria
- is treated with antibiotics, but this takes AT LEAST 6 months and success rate of treatment for second infection is lower
- M. tuberculosis can enter a dormant state -\> latent TB = evidence of infection by immunological tests but no clinical signs/symptoms of active disease
65
What sexually transmitted diseases must be reported in Europe if there is an outbreak?
- Chlamydia trachomatis infection - gram -ve
- gonorrhoea -\> Neisseria gonorrhoeae - gram -ve
- syphilis -\> Treponema pallidum - gram -ve
- Hepatitis B and C - viral
- HIV/AIDS - viral
66
Describe Chlamydia trachomatis.
- obligate intracellular pathogen -\> cannot culture it outside host cell
- most frequent STI in Europe with around 350.000 cases/year (infection likely higher due to underreporting)
- can cause eye infections -\> 84 million people infected and 8 million visually impaired -\> responsible for more than 3% of the world’s blindness
67
How does Neisseria gonorrhoeae establish infection?
- establishes infection in the urogenital tract by interacting with non-ciliated epithelial cells
- important virulence factors and traits are pilli and antigenic variation as well as being able to escape detection and clearance by the immune system
68
Name the 3 most common food and waterborne bacterial disease in Europe and the most common globally.
o campylobacteriosis -\> Campylobacter sp., mostly C. Jejunio
o salmonellosis -\> Salmonella sp.
o cholera -\> Vibrio cholerae
- listeriosis -\> Listeria monocytogenes
69
Describe campylobacter sp..
- most commonly reported infectious GI disease in the EU -\> you have to consume the live organism -\> infection is most likely through undercooked poultry
- usually sporadic cases and not outbreaks
- small children of 0-4 years are the highest risk group
- virulence factor -\> adhesion and invasion factors, flagella motility, type IV secretion system and toxins
70
Describe salmonella sp..
- one of the most common GI infections in the EU -\> mainly due to undercooked poultry
- otbreaks are seen
- highest infection rate in small children (0-4 years)
71
What is the virulence of salmonella sp.?
o type III secretion systems encoded on pathogenicity islands (SPI)
o salmonella enterica has type III secretion system
- SPI1 -\> required for invasion
- SPI2 -\> intracellular accumulation
72
Describe vibrio cholerae.
- cholera is an acute, severe diarrheal disease -\> without prompt rehydration, death can occur within hours of the onset of symptoms
- last outbreak was in Haiti, and has caused many deaths
73
What are the important virulence factors of vibrio cholerae?
- type IV fimbria
- cholera toxin carried on a phages -\> makes eukaryotic cells produce high levels of cyclic AMP (cAMP) -\> activates a transporter, resulting in chloride ions EFFLUX from the cell -\> water and sodium leaves the cell -\> DIARRHOEA -\> people die from the dehydration
74
Describe Listeria monocytogenes.
- risk groups are the immunocompromised, elderly, pregnant women and their foetus
- listeria can enter non-phagocytic cells and cross three tight barriers due to its motility -\> intestinal barrier, BBB and materno/foetal barrier
75
State some of the emerging and vector-borne diseases whihc must be reported in Europe.
- malaria - parasite
- plague -\> Yersinia pestis - gram negative -\> not a problem anymore really
- SARS - viral
- yellow fever - viral
- Q fever -\> Coxiella burnetti - gram negative
76
What vaccine prevntable diseases outbreaks must be reported in Europe?
- diphtheria -\> Clostridium diphtheria- gram positive
- invasive Haemophilus influenzae disease - gram negative
- invasive meningococcal disease -\> Neisseria meningitidis - gram negative
- invasive pneumococcal disease (IPD) -\> Streptococcus pneumoniae - gram positive
- pertussis -\> Bordetella pertussis - gram negative
- Measles, Mumps and Rubella - viral
- polio - viral
- rabies - viral
- tetanus -\> Clostridium tetani - gram positive
77
What bacteria are the major causes of hospital/healthcare acquired infections?
o **E**nterococcus faecium -\> vancomycin resistance
o **S**taphylococcus aureus -\> methicillin resistant (MRSA)
o **C**lostridium difficile -\> can establish infection due to previous antibiotic treatment
o **A**cinetobacter baumanii -\> highly drug resistant
o **P**seudomonas aeruginosa -\> multi drug resistant
o **E**nterobacteriaceae -\> pathogenic E. coli (multi drug resistant), Klebsiella pneumoniae (multi drug resistant), Enterobacter species (multi drug resistant) etc
78
Describe pathogenic E. coli.
- most frequent cause of bacteraemia by a gram-negative bacterium
- most frequent cause of community and hospital acquired UTI
- increase in multi-drug resistant strains -\> resistance to 3rd generation cephalosporsins as high as 20% in some countries and most isolates that are resistance to cephalosporin express the extended spectrum beta lactamase
- still sensitive to carbapenems
79
Describe cephalosporins.
- class of beta-lactam antibiotics -\> e.g. penicillin
- target pathway = inhibition of peptidoglycan synthesis
- target protein = inhibit the activity of penicillin binding proteins (PBPs)
- resistance to cephalosporins arises from extended spectrum beta lactamases encoded on a plasmid -\> cleave the cephalosporin antibiotic
80
Describe carbapenems.
- class of beta-lactam antibiotics
- target pathway = inhibit peptidoglycan synthesis
- target protein = inhibit the activity of penicillin binding proteins (PBPs)
- resistance to carbapenems arisse from the carbapenemase enzyme, blakpc encoded on a transposon -\> enzyme cleaves the carbapenem antibiotic
81
Describe Klebsiella pneumoniae.
- important cause of UTI and respiratory tract infections
- risk group are immunocompromised patients
- 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 US
82
Describe Pseudomonas aeruginosa.
- important cause of infection in immunocompromised patients
- high proportions of strains are resistant to several antimicrobials -\> in ½ of EU countries resistance to carbapenems is above 10%
83
Describe MRSA.
- most important cause of antimicrobial resistance infection worldwide
- methicillin is a beta-lactam antibiotic -\> target pathway is inhibition of peptidoglycan synthesis by inhibitingthe activity of penicillin binding proteins
- resistance mechanim = expression of additional penicillin binding protein -\> PBP2A has low affinity for methicillin and can still function in the presence of the antibiotic
84
Describe Enterococcus faecium.
- third most frequently identified cause of nosocomial blood stream infections (BSI) identified in the US
- vancomycin resistance is around 60%
- resistance arises from multiple proteins (genes encoded on plasmid or transposon) resulting in the synthesis of a different PG precursor
85
Name three factors, which contribute the acquisition of hospital acquired infections.
- intervention -\> catheter etc
- dissemination
- concentration
86
True or False. Cephalosporsin is a beta-lactam antibiotic and resistance is due to production of an extended spectrum beta lactamase.
- True
87
True or False. Methicillin and carbapenem are both beta-lactam antibiotics.
- True
88
True or False. Carbapenem resistence is frequently found in Klebsiella pneumoniae.
- True
89
Describe staphulococcus aureus.
- Staphylococcus aureus is a gram positive bacterium
- produces toxins including exfoliative toxin, toxic shock toxin, and enterotoxins
- is a commensal bacteria -\> 30% of the population carry it, either in the nostrils or on the skin
- can causes skin, bone, joints and lung infections as well as sepsis
- some strains are resistant to standard antibiotics -\> MRSA
90
What is the virulence factor of staphylococcus aureus?
- panton valentine leuocidin toxin -\> produces a much more necrotising infection
91
What toxins are produced by staphylococcus aureus?
- panton valentine leuocidin toxin -\> virulence factor -\> Produces a much more necrotising infection
- exfoliative toxin -\> causes cleavage of the epidermis -\> blistering
TSST-1 toxin -\> causes sickness, fever, malaise etc. -\> organ failure -\> 50% of infections with staphylococcus aureus that produce TSST-1 toxin are related to tampons
- enterotoxin -\> a problem in food consumption
92
What are infections of the skin called?
o depends on the layer that they affect
- impetigo = infection of the top layer of the skin - stratum corneum
- ecthyma = full thickness involvement of the epidermis
- folliculitis = infection and inflammation of a hair follicle - can progress into a n abscess (then called a boli) -\> carbuncle describes multiple abscesses next to each other
93
What is impetigo?
- infection of the stratum corneum (top layer of skin) often due to staphylococcus
- results ina honey-coloured crust on an eroded base
- often occurs around the nose and mouth but can occur anywhere
94
What is bullous impetigo?
- the bacteria causing the infection makes a exfoliative toxin -\> causes cleavage of the epidermis -\> extensive blistering
- blisters are fairly superficial, easily broken and can cause erosions
95
What are ecthyhmas?
- infection involving the full thickness of the epidermis
- lesions are firmly adherent and the crust will not come off -\> surface of the skin is dying
- commonly occu after an infected wound or insect bite
96
Once a folliculitis has become an abscess what is the best treatment option?
- incise it, and let the pus out and then follow this up with antibiotics
- if the pus isn’t let out, there is a chance of breeding resistant organisms
97
What is staphylococcal scalded skin syndrome?
- condition caused by a exofoliative toxin often from staphylococcus
- patient has a staph. aureus infection somewhere in the body and the toxin has entered the blood -\> exfoliative toxin is affecting the skin, distant to the origin of the infection -\> cleavage of epidermis -\> desquamation of the epidermis
- occurs in children under the age of 5 -\> something to do with an immature immune system
- illness only affects the skin – the mucous membranes are unaffected
98
What is the treatment for staphylococcus skin infections?
- antibiotics and emollients (moisturisers) if required
- recovery will take place within a few days
99
What is toxic epidermal necrolysis?
- condition involving widespread desquamation of the skin, as a result of an allergic reaction to a drug
100
What is treponema pallidum?
- a gram negative spirochete which causes syphilis
101
What are the 3 phases of syphilis?
- primary (at 3-8 weeks) = chancre (painless ulcer) at inoculation site (genital or oral) -\> lasts a few weeks, and then heals
- secondary (at 6-12 weeks) = disseminated infection, generalised rash and lymphadenopathy -\> gets better, and enters a latent syphilis phase
- tertiary syphilis (usually years later) = skin, neurological and vascular manifestations -\> can be life-threatening
102
Describe the rash seen in secondary syphilis and state what other signs may be seen.
- usually a widespread, maculopapular, erythematous rash over the body including the palms and soles
- may also see warty lesions around the perineum, axillae and groins -\> these are called condyloma lata
103
Describe teritary syphilis.
- gummatous skin lesions are barely ever seen now, but they are ulcerating lesions of the skin (often with destruction, particularly around oro-nasal region)
- vascular abnormalities -\> most common one being thoracic aneurysm -\> involves dilatation of the thoracic aorta, causing aortic regurgitation and other vascular events
- neurosyphillis -\> dementia, depression, psychoses peripheral neuropathies, headaches etc.
104
What is the potential consequence of being pregnant while suffering from syphilis?
- can cross the placenta and infect the foetus -\> babies die (either miscarriage or still birth) or are born prematurely
105
What is the consequence of congenital syphilis?
- babies born alive have features similar to secondary syphilis -\> rashes
- some may have no features at birth, but go on to develop brain/neurological problems and bone disease
- consequences = skin ulcers, bony defects, saddle nose, blindness, deafness and notched teeth
- nowadays all pregnant mothers are screened for syphilis
106
How is syphillis treated?
- is confirmed by serological tests it is treated with penicillin antibiotics -\> responds very well
107
How many herpes viruses are there?
- 8
108
What is HHV-1 commonly known as, target cell, disease it causes and site of latency?
- common name = herpes simplex virus type 1
- target cell = muco-epithelial
- disease = oral herpes
- site of latency = neuron
109
What is HHV-2 commonly known as, target cell, disease it causes and site of latency?
- common name = herpes simplex virus type 2
- target cell = muco-epithelial
- disease = genital herpes
- site of latency = neuron
110
What is HHV-3 commonly known as, target cell, disease it causes and site of latency?
- common name = varicella zoster virus (VSV)
- target cell = muco-epithelial
- disease = chickenpox and shingles
- site of latency = neuron
111
What is HHV-4 commonly known as, target cell, disease it causes and site of latency?
- common name = epstein-barr virus (EBV)
- target cell = B cell
- disease = infectious mononucleosis - glandular fever
- site of latency = B cell
112
What is HHV-8 commonly known as, target cell, disease it causes and site of latency?
- common name = Kaposi sarcoma ass herpes virus
- target cell = lymphocytes
- disease = Kaposi's sarcoma
- site of latency = B cells
113
What is the clinical presentation of herpes simplex virus infection?
- vesicular rash for around 2 weeks
- eczema herpeticum - if the patient has eczema
- herpes encephalitis
114
What is a rarer first presentation of herpes simplex virus?
- stomatitis = inflammation of the mouth
115
What is the treatment for herpes simplex virus?
- acyclovir
- if it is eczema herpeticum = intravenous antibiotics, intravenous acyclovir, emollients and topical steroids
116
Describe herpes zoster.
- herpes zoster = shingles
- after a period of dormancy the HHV-3 will reactivate
- usually results in the a monolateral rash down one dermatome -\> can be bullous
- if it involves the nasociliary branch of the opthalmic nerve it can lead to blindness
117
What are the 2 types of superficial skin fungal infections?
- dermatophytes - type of mould
- yeasts
118
What are dermatophytes?
- e.g. Trichophyton rubrum
- live off and grow in keratin
- long hyphae and grow from tip
119
What type of infections are caused by dermatophytes?
- cause tinea -\> this is suffixed by the name of the body part
- e.g. tinea unguium is a dermatophyte infection of a nail
120
What is tinea unguium?
- dermatophyte fungal infection of the nails resulting in a yellow, crumbly nail
121
What is the treatment for tinea unguium?
- 3 month course of anti-fungal tablets -\> cream wouldn't work as creams cannot penetrate deep enough into the nail matrix
122
What is tinea capitis?
- dermatophyte infection of the scalp only occurs in children, particularly Afro-Caribbean’s -\> adults have anti-fungal chemicals in the sebum of their hair, whereas children do not
123
What is the treatment of tinea capitis?
- orally anti-fungals -\> topical treatment wouldn't penetrat edeep enough
124
What is tinea manuum?
- another name for ringworm -\> common in people who regularly handle animals such as rabbits and guinea pigs
125
What is tinea pedis?
- dermatophyte infection of the foot
126
What is tinea crusis?
- dermatophyte fungal infection of the groin region
127
What is tinea facei?
- dermatophyte fungal infection of the face
128
Describe candida intertrigo.
- seen in the mouth, genital area, under the breast and in the axilla
- you see satellites around the main infection
- treated with a topical anti-fungal
129
Describe scabies.
- scabies = Sarcoptes scabei
- is a human to human disease (spread between humans by direct, skin to skin contact)
- mites and eggs cannot survive off the patient for very long
- will often have a widespread rash
- crusted scabies = patient is immunosuppressed, and has thousands of mites on the skin
- female mite burrows just under the stratum corneum (surface of the epidermis)
- typically, a scabies infection involves 15-20 mites on the body -\> can be found by looking for their burrows -\> are around half a centimetre long, and slightly wiggly and have a black dot at one end
130
What are the common sites of burrows in scabies?
131
How is scabies treated?
- an insecticide cream, put on all over the body -\> cream must be left on the body for 12 hours
- is repeated 5 to 7 days later - this should clear it
- all the household contacts should be treated at the same time
- washing all bedding and clothes at a high temperature is also recommended
132
What are the 2 branches of the adaptive immune response?
- cellular = T cells
- humoral = antibodies
133
What kind of pathogen are viruses?
- obligate intracellular pathogens
- any of their proteins are seen as 'foreign' so if causing acute infection they are cleared by T cells but if they cause chronic infection they must have a mechanism to avoid detection
134
Describe MHC presentation of a virus.
- cells are constantly looking at what’s inside them -\> tend to chop up pieces of viral and cellular peptides in the proteasome
- these get loaded on to a MHC Class I molecule which is transported up to the cell surface, where it presents these peptide fragments to the outside world
- if a T cell that bears a specific T cell receptor that matches those peptides, T cell will bind this cell the CD8 T cell will then kill this cell -\> engagement of the T cell receptor and the CD8 molecule will trigger a cytotoxic response (release of granzyme)
135
What is the role of TAP?
- proteasome chops up a protein into peptides -\> these peptides are loaded into the endoplasmic reticulum through a molecule called **TAP**
136
Name 3 viruses which evade antigen loading to TAP and how they do so.
**- EBV:** EBNA1 cannot be processed by the proteasome
**- HSV:** ICP47 blocks access of the processed peptide to TAP
**- CMV:** US6 stops ATP binding to TAP, preventing translocation
137
What is the role of tapasin?
- foreign molecule is transferred from TAP to a second molecule, called **tapasin** -\> **tapasin** places the peptide into the groove of the MHC class I molecule before it is transported up to the cell surface
138
Name 2 viruses which modulate tapasin function and therefore prevent MHC transport and state how they do so.
**- CMV:** US3 binds tapasin and prevent peptides being loaded to MHC
**- Adenovirus:** E3-19K prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum
139
How does Kaposi's sarcoma virus avoid immune detection?
o interferes with MHC presentation at the cell surface
- kK3 protein induces polyubiquitinylation and internalisation of MHC
- if the MHC reaches the cell surface, the kK3 protein covers it with ubiquitin, and pulls it back
- T cell receptor will NEVER ‘see’ the MHC presented peptide -\> result is a loss of the MHC Class I molecule at the cell surface -\> from the internalised endosome, MHC is passed to lysosomes where it is degraded
140
What is the normal mechanism of NK cells?
- mormal healthy cells display MHC at their surface
**- cells that don’t display MHC are detected by NK cells and killed**
- viruses that disrupt MHC presentation would end up being killed by NK cells
141
How have viruses evolved to avoid death by NK cells?
- encode MHC analogues (CMV gpUL40) or upregulate MHC to avoid this
142
Define influenza antigenic drift.
- continued rapid evolution driven by antigenic pressure from the host
143
What is meant by HIV quasispecies?
- the appearance of HIV is massively diverse (many different versions and strains)
144
What are the evolutionary pressures driving influenza antigenic drift?
- antibodies usually work by blocking infection -\> pre-existing antibodies that are specific for the surface of the virus will coat the virus before it has a chance to latch onto the cell receptor -\> virus will not infect the cell, and no new viruses will be made
- this is called sterilising immunity -\> enough antibody (that matches the virus) exists in the host body to prevent the initiation of secondary infection
145
Describe the process of antigenic drift.
- due to the selection pressures viruses evolves, so even if we have produced antibodies against a virus, it may not be effective in preventing re-infection
- one or two amino acid changes may change the way that the antibody sees the epitope -\> virus is now capable of infecting people, even if they were infected before/have been vaccinated against the virus
146
Define influenza antigenic shift.
- introduction of new subtype usually from an animal source
147
How might a universal flu vaccine be produced?
- by causing our immune system to upregulate its antibody response to the stem of the haemagglutinins instead of its current targetting of the heads of the haemagglutinins
- as the stem doesn't change (too importnat to the viruses life) this would provide a universal vaccine
148
How is HIV so effective at evading antibodies in HIV?
**o HIV env gene** encodes gp120 protein (these form spikes), which resists neutralization because:
- there are very few gp120 spikes on the viral surface -\> large space between spikes prevents, which prevents antibody crosslinking
- extensive glycosylation of gp120 masks antibody epitopes (sugar acts like an umbrella) -\> functionally important parts of the molecule (e.g. CD4 binding site) are poorly accessible
- CD4 is the receptor that gp120 binds to, in order for HIV to enter cells -\> there are redundant amino acids that are visible to B cell receptor and antibodies
- surface amino acids are being changed all the time to evade antibody attack -\> huge variation in the redundant amino acids means that most antibodies are highly clade specific
149
What is the problem with neutralising HIV using antibodies?
- somehow want to encourage a person to actively produce antibodies that neutralise all the different strains that any particular virus -\> antibodies that can cross-react with many HIV strains do exist alongside virus in people -\> bNabs produced as biological therapeutics can control viral load
- HIV isevolving very fast -\> if you give an infected person a broadly neutralising antibody, to begin with, it works and the viral load is controlled however later on, the viral load increases again -\> virus has selected for resistant viruses
150
How does rhinovirus continually cause the common cold?
- exists as more than 120 antigenically distinct serotypes -\> never going to have them all and making a vaccine against all of them is improbable
151
Describe the polio vaccine.
o polio virus has a similar structure to rhinovirus but only has 3 distinct serotypes
o two vaccines for polio -\> have come close to eliminating poliovirus from the world -\> 1 serotype is already eradicated
- a live, inactivated vaccine
- a dead vaccine
- are 3 serotypes of poliovirus required a trivalent poliovirus vaccine -\> 3 serotypes are mixed in approriate quantities to bring a response to all 3 -\> only 2 now due to the eridication of one strain
152
What is dengue haemorrhagic fever?
- only get the fever on a second bout of dengue infection -\> first time you are fine
**o causes leakage of plasma from the capillaries which leads to:**
**- increased haematocrit**
**- increased red cell count**
**- decrease in protein in the blood**
- has a tendency to cause severe bruising and bleeding
- DHF is detected by increased RBC count and decreased serum protein
- patient deteriorates even after the fever drops: shock
- treat with **IV fluids** but no specific treatment
153
What is antibody dependent enhancement of dengue virus?
- if you have been infected with one serotype of dengue, you will develop antibodies against it
- if another serotype infects you, your antibodies will bind to but not neutralise the new serotype of dengue -\> will cause antibody dependent enhancement of the current dengue serotype causing dengue haemorrhagic fever -\> the antibodies become HARMFUL by giving the virus entry into cells via a new route
- heterotypic antibody bound to the virus can be detected by Fc receptors on immune cells (e.g. monocytes)
- antibody-virus complex enters the monocyte -\> dengue virus on its own wouldn’t normally be able to do this
- viral replication takes place in the monocyte -\> monocytes release many IFNs, leading to cytokine storm
154
What are the complications of a dengue vaccine?
- it would need to make fully neutralising antibodies against all four serotypes
- a vaccine that stimulated antibody production against one serotype, the first time they get infected with a different serotype could be fatal
155
Describe virus-mediated immunosuppression using an example.
- some viruses lead to immunosuppression
- measles virus **infects CD150 positive cells**, including **memory lymphocytes** and erases immunological memory -\> measles virus infection results in a 2-3 year decrease in immunological memory -\> leads to morbidity and mortality from other diseases
- why it is so important to be vaccinated against measles
156
Which answer 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
o E
- B is true because most cultures have some innate immune system element to them to help the growth of targetted cells
157
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 degradatio
C: preventing the loading of peptides by TAP
D: inducing a cytokine storm
E: encoding MHC homologues
- B
- other affect adaptive immune system
158
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 contain host proteins (control complement activation)
E: Activate interferon induction pathway through cGAS and STING
- C
- A, B and D are found in both types and E is more likely in DNA viruses
159
Which is NOT true concerning the interplay between Hepatitis C virus and the immune systems?
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 – this determines chronicity
C: NS3/4A protease cleaves MAVS and prevents activation of interferon
D: It encodes a protein called vif that counteracts the ISG APOBEC and prevent it from inducing hypermutation of the viral genome
E: A genetic polymorphism in IL28b results in non-responsiveness to interferon treatment
o D
- D is a mechanism found in HIV not hepatitis C
160
Define vector.
- an organism, typically a biting insect or tick, that transmits a disease or parasite from one animal or plant to another
161
Define parasite.
- an organism living in (endo)/on (ecto) the host and dependent on it for nutrition, causing damage
- can be endoparasites or ectoparasites
162
What are the 2 classes of endoparasites?
- protozoa -\> single-celled organisms
- metazoa -\> multicellular organisms - Helminths/worms
163
Describe protozoa.
**- single-celled e_ukaryotes_ -\> their genome is within a nucleus, and they have complex organelles in the cytoplasm**
- pathogenesis (mechanism of disease) varied
- some have vectors (e.g. malaria - human to human transmission via a mosquito) other by the faecal-oral route
- not characterised by eosinophilia
164
Describe metazoa.
**- multicellular organisms -\> Helminths/worms**
- free living, intermediate hosts and vectors
- some just inhabit the gut (geohelminths) others invade tissues
- characterised by eosinophilia (if the organism invades the blood)
165
What are the 4 groups of protozoa?
**- Amoebae:** *Entamoeba* *histolytica,* *Entamoeba* *dispar*
**- Coccidian**: *Plasmodium* species,*Toxoplasma,* *Cryptosporidium*
**- Ciliates**: *Balantidium* *coli*
**- Flagellates**: *Trichomonas,* *Giardia,* *Trypanosoma,* *Leishmania*
166
Name 2 amoebae protozoa.
- Entamoeba histolytica
- Entamoeba dispar
167
How do you become infected with a amoebae protozoa?
- ingestion of mature cysts in food or water, or on hands contaminated by faeces
168
How big of a problem are amoebae protozoa?
- about 10% of the world’s population is infected with *E. histolytica -\> 90% are asym*ptomatic but the remaining 10% produce a spectrum of disease, varying from dysentery to amoebic liver disease
- 3rd most common cause of death or parasitic infections (after schistosomiasis and malaria) -\> common in South/Central America, and in West/South East Asia
169
Describe the pathway/infectious route of amoebic protozoa.
- humans are the only reservoir in amoebic infection
- infection occurs by ingestion of mature cysts in food or water, or on hands contaminated by faeces
- cysts of *E.* *histolytica* enter the small intestine and release active amoebic parasites (trophozoites) -\> invade the epithelial cells of the large intestines, causing flask-shaped ulcers -\> can spread from the intestines to other organs, e.g. liver, lungs and brain, via venous system
- asymptomatic carriers pass cysts in faeces and the asymptomatic carriage state can persist indefinitely
- cysts remain viable for up to 2 months
170
Describe the pathogenesis of amoebic protozoa.
- cysts of *E.* *histolytica* enter the small intestine and release active amoebic parasites (trophozoites) -\> invade the epithelial cells of the large intestines, causing flask-shaped ulcers
- infection can spread from the intestines to other organs, e.g. liver, lungs and brain, via venous system -\> causes amoebic liver disease as well as respiratory and neuronal issues
171
How can amoebic protozoa infection be diagnosed?
- diagnosed by direct microscopy -\>\> look for them on a slide of faeces
- a wet mount -\> cysts are spherical and measure 12-15 micrometres
- mature cyst has 4 nuclei while an immature cyst contains only 1-3 nuclei
172
What species cause malaria?
- plasmodium species -\> part of the coccidia family
173
What are the symptoms of malaria?
- fever, headache, chills, vomiting, muscles pain and **paroxysm** (fever which goes up and down) in cycle of 4 to 8 hours
- can appear as early as 7 days but the time between exposure and signs of illness can be as long as one year - depends on the type of plasmodium -\> e.g. 9 to 14 days for *Plasmodium falciparum*
174
What are the complications of malaria?
**- severe anemia (due to destruction of red cells) – MOST COMMON**
**- cerebral malaria (swelling of the brain, seizures and coma) – MOST COMMON**
- liver failure
- shock
- pulmonary oedema
- abnormally low blood sugar
- kidney failure
- swelling and rupturing of the spleen
175
What is the treatment for 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
176
How is malaria diagnosed?
- blood film using giemsa stained microscopy -\> can detect the type of the malaria by looking at the shape of the parasite
- rapid test is available commercially -\> antigen detection tests -\> is expensive and less sensitive
177
Name 3 coccidia protozoa infections.
o plasmodium species
o toxoplasma
o cryptosporidium
- are most zoonoses
178
How does toxoplasma infect humans?
- eating undercooked meat of animals harboring tissue cysts
- consuming food or water contaminated with cat feces
- contaminated environmental samples
- blood transfusion
- organ transplantation
- transplacentally from mother to foetus
179
What does taxoplasma cause?
o toxoplasmosis
- mild disease in immunocompetent individuals -\> fever, swollen lymph nodes, headaches, sore throat
- however, in pregnancy -\> toxoplasmosis poses serious danger for the foetus
180
What can develop in immunocompromised patients infected with toxoplasma?
- central nervous system disease
- brain lesions
- pneumonitis
- retinochoroiditis
181
Describe cryptospordidium infection.
- if you are healthy, you are unlikely to even realised you have been infected
- if you are immunosuppressed, it causes many problems -\> illness is very common in HIV patients
- causes diarrhoea, fever, nausea and vomiting in humans
182
How is cryptosporidium diagnosed?
- stool examination
183
How is cryptosporidium treated?
- fluid rehydration to make up for fluid lost due to diarrhoea
184
Name a ciliate protozoa.
- Balantidium coli -\> causes balantidiasis
185
Describe Balantidium coli.
- reservoir hosts include pigs, rodents and primates -\> is a worldwide distribution
- ciliates are asymptomatic most of the time but, it is a problem in HIV positive patients -\> may experience more severe signs and symptoms
- symptoms = persistent diarrhea, dysentery, abdominal pain, weight loss, nausea, and vomiting. If left untreated, perforation of the colon can occur
- diagnosis = stool examination
- treatment = fluid replacement
186
Name 3 flagellate protozoa.
- giardia -\> giardia lamblia
- trichomonas
- leishmania
187
How can Giadria lamblia infection be prevented?
o is a water-bourne protozoal infection causing Giardiasis
- 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
- 2% of adults and 6% to 8% of children in developed countries worldwide
- 33% of people in developing countries
188
What are the symptoms of Giardia infection?
- most people infected with *giardia* have no symptoms -\> asymptomatics can still transmit cysts
- acute symptoms = diarrhea, greasy stools that tend to float, stomach or abdominal cramps, upset stomach or nausea/vomiting, dehydration (loss of fluids)
189
How is Giardia infection diagnosed?
- stool examination
190
How is Giardia infection treated?
- metronidazole or tinidazole
191
How is trichmonoas transmitted?
**- transmitted sexually -\>** most common, curable, non-viral STI in the UK -\> in adults it is exclusively transmitted sexually
- in women the organism is found in the vagina, urethra and para-urethral glands
- in men infection is usually of the urethra
192
What are the symptoms of trichomonas?
- 10-50% are asympotomatic
o females = vaginal discharge, vulval itching, dysuria, or offensive odour (not specific for TV) -\> occasionally the presenting complaint is of low abdominal discomfort or vulval ulceration
o males = discharge and/or dysuria
193
What are the complications of trichomonas?
- detrimental outcome on pregnancy and is associated with pre-term delivery and low birth weight.
- HIV -\> is growing evidence that trichomonas infection may enhance HIV transmission and there may be an increased risk of TV infection in those that are HIV positive
194
How is trichomonas infection diagnosed?
- microscopy -\> detection of motile trichomonads in swab/urinem,
- trichomonas rapid test
195
How is trichomonas treated?
- metronidazole
196
Describe helminths metazoa infections.
- Helminths are complex multicellular parasites
- cycles may involve insect vectors and intermediate hosts -\> for most, humans are the definitive host
- adult worms cannot multiply in man
- lay eggs, microfilaria and larvae
- HIGHEST worm burdens are in school-aged children
197
What are the different types of worms?
- roundworms = Nematodes -\> *Ascaris,* hookworm*, Filaria, Strongyloides*
- flatworms = Cestodes -\>*Taenia* (tapeworms)
- flukes = Trematodes -\> Schistosoma
198
Describe the symptoms and pathology of ascariasis nematodes.
- infection with *Ascaris* *lumbricoides* often causes no symptoms but a large number of worms may cause abdominal pain or intestinal obstruction
- adult worms feed on the contents of the small intestine and in heavy infections may compound problems in malnourished individuals (especially children)
- migration of larvae may cause localized reactions in various organs -\> penetration of the larvae from capillaries into the lungs can lead to Loeffler's pneumonia -\> causes pools of blood and dead epithelial cells clog air spaces in the lungs -\> resulting bacterial infections can be fatal
199
How is a nematode infection diagnosed?
- stool examination -\> eggs have a very distinct shape
200
What is the treatment for nematode metazoa infection?
- albendazole and mebendazole
201
How long are nematodes?
- ascariasis = 15-30cm
- hookworm = 1 cm
202
What are the symptoms and what is the pathology of hookworm nematodes?
- iron deficiency anemia -\> caused by blood loss at the site of intestinal attachment of the adult worms -\> can be accompanied by cardiac complications
- gastrointestinal and nutritional/metabolic symptoms can also occur
- local skin manifestations can occur during penetration by the filariform (L3) larvae
- respiratory symptoms can be observed during pulmonary migration of the larvae
203
What parasites cause lympathic filariasis and how do they do so?
- brugia malayi and wucheria bancrofti -\> both are nematodes
- organisms can block lymphatic vessels -\> leading to massive limbs
- lymphatic obstruction (especially in the legs) can progress to elephantiasis -\> can also occur in arm, breast, scrotum
204
How are brugia malayi and wucheria bancrofti trnasmitted to humans?
- mosquito
205
How does the diagnosis and treatment for brugia malayi and wuchereria bancroft different to other nematodes?
- diagnosis = microfilariae are found mainly in the peripheral blood and can be found at peak amounts from 10 p.m. to 4 a.m. -\> during the day, they are present in the deep veins, and during the night, they migrate to the peripheral circulation -\> **blood smear/antigen detection with a immunochromatic test**
- treatment= albendazole and **ivermectin**
206
Describe Loa Loa infection.
- causes loaiasis
- worm is mainly found in the eye and it can be seen moving in the eye and in the patient’s vision
- transmitted by a fly
- confined to Africa
- adult worm live in man for 4-12 years if untreated
207
Describe Taenia spp. infection.
- humans are the only definitive hosts for tapeworms -\> *T.* *solium,T. asiatica* (pork) and *T.* *saginata* (beef)
- can be seen in the faeces as a segmental, flat worm
- worm can be ingested by eating raw meet (eggs in the food can enter the body)
- eggs of these worms can survive for days to months in the environment
208
What are the symptoms of Taenia/tapeworm infection?
- most people have no symptoms or mild symptoms
- patients with T. saginata taeniasis often experience more symptoms (size of the worm up to 10m) that those with T. solium or T. asiatica (3 m)
o can cause digestive problems including abdominal pain, loss of appetite, weight loss, and upset stomach -\> most visible sign of taeniasis is the active passing of tapeworm segments
209
How is the diagnosis of Taenia infection made?
- segment in the stool or identification of distinct eggs in stool
210
How is Taenia infection treated?
- praziquantel
211
What is the most common cause of acquired epilepsy in the world?
- Taenia solium -\> can cross the BBB
212
What causes schistosomiasis?
- trematodes -\> S. mansoni, haematobium, japonicum etc.
213
What are the symptoms of schistosomiasis/trematode infection?
- within days = rash or itchy skin
- within 1-2 months = fever, chills, cough, and muscle aches -\> most people have no symptoms at this early phase of infection
- when adult worms are present, the eggs that are produced usually travel to the intestine, liver or bladder, causing inflammation or scarring -\> children who are repeatedly infected can develop aenemia, malnutrition, and learning difficulties
214
How is schistosomiasis diagnosed?
- stool or urine samples
215
How is schistosomiasis treated?
- praziquantel (but this has a lot of side effects)
- the snail intermediate host can be killed to stop the cycle of the parasite
216
Name 2 ectoparasites.
- scabies
- lice
217
Describe scabies.
- scabies (sarcoptes scabiei) is an ectoparasite
- transmission requires direct, skin-to-skin contact
- female scabies parasite deposits eggs in the skin, forming burrows -\> eggs hatch beneath the skin, and release larvae -\> causes itching
- diagnosis for scabies is looking for the appearance of a rash and burrows on the skin
- treatment involves scabicides (drugs that are specific to scabies)
218
Name 3 lice.
* - Pediculus humanus capitis* = head louse
* - Pediculus humanus corporis* = body louse, clothes louse
* - Pthirus pubis* = "crab" louse, pubic louse
219
What are the 3 stages to a lice life cycle?
- eggs, nymphs and adult
- transmission by direct contact = must be close proximity between individuals for transmission
220
What is the vector for leishmania?
- the sandfly
221
Describe the 2 forms of leishmania.
**- Promastigote** -\> form that is transmitted by the sandfly
- has a flagellum
- can be culture
**- Amastigote** -\> form that is achieved inside the phagocytic cells of the host
- form the leishmania within humans or other vertebrate host cells
- have resorbed their flagellum and are no longer motile
222
What are the 2 major forms of leishmaniases?
- visceral
- cutaneous
223
What are the symptoms of visceral leishmaniasis?
- characterised by irregular fever, weight loss, swelling of liver and spleen, anaemia -\> affects the internal organs
- MAIN SYMPTOMS = hepatosplenomegaly, anaemia and malnourishment
- can be fatal
- is also called black fever
224
What are the risk factors for visceral leishmaniasis?
- are 30-100 subclinical infections for every overt, symptomatic VL case
- risk factors for development of disease = malnutrition, immunosuppression, HIV co-infection
225
How is visceral leishmaniasis diagnosed?
- diagnosis is based on case definition: *“a* *person* *who* *presents* *with* *fever* *of* *more* *than* *two* *weeks* with *splenomegaly* *and/or* *lymphadenopathy or* *either* *of* *weight* *loss,* *anaemia* *or leucopenia* *while* *living* *in* *a* *known* *VL* *endemic* *area* *or* *having* *travelled* *to* *an* *endemic* *area”*
**- parasite and antibody detection** are more commonly used when available
226
What is the treatment for leishmaniasis?
- sodium stibogluconate (SSG) or meglumin antimoniate (monotherapy)
227
What are the 3 forms of cutaneous leishmaniasis?
- localised
- diffuse
- mucocutaneous
228
Describe localised cutaneous leishmaniasis.
- skin lesions on exposed body parts, often self-healing
- can create serious disability and scars immunity to reinfection
- in localised disease, a portion of the skin begins to crust and it will eventually heal
- are left disfigured -\> children cannot go to school (bullying), women cannot marry easily -\> causes many social problems
- once someone is exposed to the disease, they are subsequently immunized
229
Describe diffuse cutaneous leishmaniasis.
- disseminated lesions characterised by nodules (non-ulcerating lesions)
- resembles leprosy difficult to treat, no spontaneous healing, frequent relapses -\> because the nodules do not ulcerate, they never heal
- nodules are FULL of parasites
- no controlling treatment -\> lots of social stigma due to the lesions looking like leprosy
230
Describe mucocutaneous leishmaniasis (aka mucosal leishmaniasis).
- disfiguring, destroys mucous membranes
- caused by *L. braziliensis*
- can destroy the mucosa of the nose and mouth, and can therefore be very severe -\> causes malnutrition because it hurts to eat
- no spontaneous healing, and relapse take place
