Microbiology Flashcards
1
Q
What is the difference between a pathogen and a commensal?
A
A pathogen is an organism that is capable of causing disease, a commensal colonises the host but under normal circumstances doesn’t cause disease.
2
Q
What is an opportunist pathogen?
A
A microbe that only causes disease if host defences are compromised, e.g. E coli is normally present in the gut, but can cause a UTI if it gets into the urinary tract.
3
Q
Which areas of the body are open to bacterial colonisation?
A
Nasal and oral passages
GI tract
Vagina
A small portion of the urethra
4
Q
What shape are cocci?
A
Round
5
Q
What shape are bacilli?
A
Rod-shaped
6
Q
What are the different configurations of cocci?
A
Single
Diplococci
Chains
Clusters
7
Q
How do flagellae help microorganisms?
A
Motility - they can help organisms ‘swim’ towards target cells
8
Q
How do pili/fimbriae help pathogenic organisms?
A
They help the microbe to adhere to surfaces, allowing them to introduce toxins to a host cell.
9
Q
What colour do gram positive bacteria appear following gram stain?
A
Purple
10
Q
What colour do gram negative bacteria appear following gram stain?
A
Pink
11
Q
What stain can be used if bacteria don’t stain with gram?
A
Ziehl-Neelsen stain
12
Q
What type of bacteria don’t stain with gram and why?
A
Mycobacteria have a waxy cell wall, which gram stain struggles to penetrate
13
Q
Which compound is found on the inner membrane of gram negative bacteria that the immune system is designed to recognise?
A
Lipopolysaccharide (endotoxin)
14
Q
Some bacteria create free spores with their DNA inside, which can then be aerosolised. Name a bacterium that does this.
A
Anthrax
15
Q
What diagnostic tool cannot be used for identifying microbes with a long doubling time?
A
Cultures - if the microbe has a long doubling time (e.g. M tuberculosis 24 hours), it would take months to become visible on culture.
16
Q
Exotoxins are proteins secreted by which type of bacteria?
A
Both gram positive and gram negative
17
Q
How can exotoxins be disabled?
A
They can be unfolded using heat –> disabled
18
Q
What are the consequences of the rapid replication of bacterial DNA?
A
Frequent mutation, which can lead to antibiotic resistance
19
Q
What are the possible structures of bacterial DNA?
A
Either a singular closed circular chromosome or a plasmid
20
Q
How can bacteria share genetic information?
A
Via bacterial conjugation - a sex pilus is formed between the donor and recipient, which is a hollow tube through which genetic information can be passed.
Or via plasmids
21
Q
What are the features of Staphylococci?
A
Gram positive (purple) cocci, which grow in clusters, facultative anaerobic
22
Q
What test can be performed to categorise Staphylococci?
A
Coagulase
23
Q
Is Staph aureus coagulase positive or negative?
A
Positive
24
Q
Where is Staph aureus normally found?
A
In the nose and skin
25
What are the virulence factors of Staph aureus?
- Some strains produce pore-forming toxins e.g. alpha haemolysin, proteases, TSS toxin and protein A (which makes antibodies bind in the wrong direction, preventing opsonisation)
- MRSA is resistant to beta-lactams, gentamicin, erythromycin and tetracycline
26
Name two types of coagulase negative Staphylococci
Staphylococcus epidermis
| Staphylococcus saprophyticus
27
Why does Staphylococcus epidermis cause infections in prostheses?
Its main virulence factor is the ability to form persistent biofilms, e.g. on artificial heart valves
28
Why does Staphylococcus saprophyticus cause acute cystitis?
It adheres to the bladder because of haemagglutinin
29
How do Streptococci appear in culture?
Gram positive (purple), growing in long chains
30
What test can be used to differentiate between different types of streptococcus?
Haemolysis
31
What is the difference in appearance between alpha and beta haemolysis on blood agar?
Alpha haemolysis - only partial clearing around the colony, greenish appearance
Beta haemolysis - complete clearing of blood around the colony
32
What does Lancefield grouping differentiate by?
Carbohydrate cell surface antigens
33
How can we check Lancefield group?
Adding antisera to see which one causes clumping (indicates recognition)
34
Streptococcus pyogenes is which Lancefield group?
Group A
35
What are the virulence factors of S pyogenes?
```
Exported factors:
Enzymes e.g. hyaluronidase, streptokinase (breaks down clots), C5a peptidase
Surface factors:
Capsule - hyaluronic acid (protection)
M protein (encourages complement degradation)
Toxins:
Streptolysins O and S (bind cholesterol)
Erythrogenic toxin SPeA
```
36
What infections are caused by Streptococcus pyogenes?
```
Wound infections, e.g. cellulitis
Tonsillitis, pharyngitis
Otitis media
Impetigo
Scarlet fever
```
37
Strep pneumoniae is a normal commensal in the oropharynx present in ~30% of the population. What conditions can it potentially cause?
Pneumonia
Otitis media
Sinusitis
Meningitis (infants and elderly)
38
What are the virulence factors of Strep pneumoniae?
Capsule (polysaccharide, antiphagocytic)
Inflammatory wall
Cytotoxin - pneumolysin
39
What conditions can be caused by viridans group Streptococci?
Dental caries - often present in oral cavity
| Endocarditis if it gets into the bloodstream
40
Name 4 gram positive bacilli
1. Listeria monocytogenes
2. Bacillus anthracis
3. Corynebacterium diphtheriae
4. Clostridia e.g. C tetani, C botulinum, C difficile
41
Why is lipopolysaccharide known as 'endotoxin'?
It forms the outer leaflet of the outer membrane of gram negative bacteria and is toxic to human cells, triggering an inflammatory response
42
GI infections tend to be caused by which 3 gram negative bacteria?
1. Shigella flexneri
2. Escherichia coli
3. Salmonella enterica
43
How can you identify which of the 3 bacteria has caused a GI infection?
Culture using MacConkey-lactose agar. E Coli can metabolise lactose, so will produce lactic acid, lowering the pH.
To differentiate between salmonella and shigella, use serology (shigella has no flagella, so will not show a flagella antigen)
44
What are the O, K and H antigens present on the cell surface of gram negative bacteria?
O antigen = LPS
K antigen = exopolysaccharide capsule
H antigen = flagella
45
What is the name given to antigenically distinct variants within species of gram negative bacteria?
Serovars
46
E coli is normally present in the GI tract. What are the 6 principal infections caused by pathogenic varieties of E coli?
1. Wound infections
2. UTIs
3. Gastroenteritis
4. Travellers' diarrhoea
5. Bacteraemia (can lead to sepsis)
6. Meningitis in infants (rare in the UK)
47
Why are some strains of E coli pathogenic?
They can acquire blocks of genes from other bacteria, thereby acquiring pathogenic properties
48
What is the main symptom of Shigellosis?
Severe bloody diarrhoea
49
Why is Shigella able to cause illness?
Only a small amount is required to establish infection, so only a small amount needs to survive the low pH in the stomach - allows person to person spread and also via contamination of food and water
50
How does Shigella invade the colonic mucosa?
It is taken up by a macrophage, it then induces the macrophage to apoptose and is released on the basolateral side of the epithelium, where it can infect adjacent epithelial cells, moving through the cytoplasm using actin filaments from the host cell.
Destroys epithelium and also causes inflammation as the apoptotic macrophage releases cytokines
51
What is the major virulence determinant of Shigella?
Shiga toxin, which inhibits protein synthesis and causes cell death.
52
What potentially fatal condition can be caused by the Shiga toxin?
Haemolytic urinae syndrome, if Shiga toxin is absorbed systemically. Targets kidney, microvascular thrombosis in kidney results in kidney failure and possibly death.
53
What three conditions can be caused by Salmonella enterica?
1. Gastroenteritis/enterocolitis
2. Enteric fever (typhoid/paratyphoid fever, caused by specific serovars Typhi and Paratyphi)
3. Bacteraemia (serovars Cholerasuis and Dublin) - uncommon
54
Why does salmonellosis require a high infected dose?
It does not tolerate low pH well, so a large amount is required for some to survive , infect the gut epithelium and trigger an inflammatory response.
55
How does the Typhi serovar of Salmonella cause typhoid?
- S Typhi is ingested
- Travels to the liver, spleen and bone marrow, where it multiplies
- Much larger numbers are released into the bloodstream
- The kidney and other organs are infected
- Can result in 'carrier' state for over a year if it travels to the gall bladder
- Travels to the small intestine, causing inflammation and ulceration, leading to diarrhoea and possible haemorrage/perforation
56
Where is Klebsiella pneumonaie infection usually contracted?
In hospital
57
What problems can be caused by Klebsiella pneumonaie infection?
UTIs
Pneumonia (via aspiration from the oropharynx)
Surgical wound infections
Bacteriaemia (and possibly sepsis)
Also difficult to treat as resistant to carbapenems
58
Vibrio cholerae is a facultative anaerobe that can result in severe diarrhoael disease. Which populations are most at risk?
Vibrio cholerae lives in saline environments and is commensal to planktonic crustaceans that are ingested by shellfish; therefore those living in coastal areas with poor sanitation are most at risk due to contamination of drinking water
59
Vibrio cholerae is highly infective. How is it transmitted from person to person?
Faecal-oral route
60
How can cholera be treated?
Oral replacement therapy
61
What is the major virulence determinant of vibrio cholerae?
Cholera toxin, which binds to a glycolipid receptor on an epithelial cell, resulting in continuous activation of G protein, which leads to uncontrolled cAMP production and modification of CFTR ion transporter, leading to a loss of Na+ and Cl- into the gut lumen, which results in massive loss of water.
62
Haemophilus influenzae is an exclusively human parasite, which causes opportunistic infections in which groups?
Young children and adult smokers. Can also cause pneumonia in CF, COPD and HIV patients.
63
What are the virulence determinants of Haemophilus influenzae?
Capsule - invasive strains are encapsulated, giving resistance to phagocytosis and the complement system.
LPS (endotoxin) - causes inflammation and confers some resistance to complement
64
Legionella pneumophila causes Legionnaire's disease, which results in severe inflammatory pneumonia. Which groups are at risk?
Immunocompromised
Elderly
Alcoholics
Smokers
65
Where is Legionella pneumophila found?
In man-made aquatic environments, e.g. air conditioning systems, shower heads, nebulisers, humidifiers
66
Why does Legionella pneumophila cause severe inflammatory pneumonia?
It can survive and replicate within alveolar macrophages. Therefore, once it is phagocytosed, it can recruit ER, differentiate to its flagellated form and become motile. It also upregulates pro-inflammatory genes in the alveolar macrophages, resulting in excessive influx of neutrophils into the lungs.
67
Bordella pertussis causes which disease?
Whooping cough
68
Bordella pertusses contains which two toxins?
1. Pertussis toxin, which locks S1 G protein in off state - this G protein would normally inhibit adenylate cyclase, so cAMP is massively increased
2. Adenylate cyclase haemolysin toxin, which prevents adenylate cyclase from being broken down, resulting in a massive increase in cAMP
Hypersynthesis of cAMP leads to suppression of innate immune functions, particularly phagocytosis by macrophages.
69
What is Neisseria meningitidis also known as?
Meningococcus
70
How does Neisseria meningitidis spread from person to person?
It is normally present in the nasopharynx of 5-10% of the population and normally does not cause symptoms. It can be transmitted via aerosol.
71
N meningitidis can cause septicaemia and meningitis. How does this happen?
It crosses the nasopharyngeal epithelium and enters the blood stream, which can cause septicaemia. If the bacteria cross the blood brain barrier, they can enter the CSF of the subarachnoid space and cause meningitis.
72
What are the virulence determinants of N meningitidis?
Capsule - anti-phagocytic (non-capsulated version not pathogenic)
LPS - leads to cytokine cascade and sepsis
73
Gonorrhoea is the second most common STD worldwide. Which bacteria causes it?
Neisseria gonorrhoeae (also known as 'gonococcus')
74
What are the potential complications of gonorrhoea?
Urethritis, infection of female genitalia (can lead to salpingitis and/or PID). Can also cause proctitis, gingivitis and pharyngitis depending on type of sexual activity.
75
What is the most common cause of food poisoning in the UK and US?
Campylobacter (jejuni/coli), most commonly found in undercooked poultry and unpasteurised milk
76
What conditions can be linked to infection with Helicobacter pylori?
Gastritis
Peptic ulcer disease
Less commonly - gastric adenocarcinoma, lymphoid tissue lymphoma
77
What is the most abundant commensal in the large intestine?
Bacteroides
78
Why is bacteroides often present in polymicrobial infections with enterobacteria?
The enterobacteria are facultative anaerobes; they deplete the O2, which allows anaerobes such as bacteroides to proliferate
79
What opportunistic infections are caused by bacteroides?
Usually peritoneal cavity infections such as peritonitis and intra-abdominal abscesses following tissue injury
80
Chlamydia and Chlamydophila are obligate intracellular parasites. What are the two developmental stages?
1. Elementary bodies are dormant enter the cell through endocytosis, prevent phagosome-lysosome fusion and differentiate to reticular bodies
2. Reticular bodies are metabolically active, acquire nutrients from host cell, replicate and convert back to elementary bodies (causes cell lysis, elementary bodies are then free to enter another cell)
81
The genital tract biovar of chlamydia trachomatis is the most common STD. How does it infect people?
It infects the epithelial cells of the mucous membranes of the urethra in both sexes and the vagina, where it can ascend to the uterus and ovaries, potentially causing PID and infertility.
Can also cause conjunctivitis via hand to eye transmission
82
What disease is caused by Borrelia burgdorferi?
Lyme disease
83
Lyme disease can be transmitted to humans via tick nymphs. What symptoms does it cause?
A Bull's eye rash, flu-like symptoms.
Can also disseminate to other parts of the body via the blood/lymphatic system and cause neurological problems and arthritis in the joints due to inflammation triggered by immune response.
84
What organism causes syphilis?
Treponema pallidum (spirochaete bacterium)
85
Describe the three stages of syphilis infection
1. Primary stage: localised genital infection, highly transmissible
2. Secondary stage: systemic infection resulting in skin rash, swollen lymph nodes, joint, pain, muscle aches, fever, headache. Still highly transmissible.
3. Tertiary stage: Granulomas in soft tissue and bone, cardiovascular syphilis, neurosyphilis. Non-infectious at this stage.
86
What is the most common mycobacterial infection?
Tuberculosis (mycobacterium tuberculosis)
87
What is the standard therapy for tuberculosis infection?
Isoniazid, rifampicin, pyrazinamide and ethambutol for two months followed by isoniazid and rifampicin for a further four months
88
What are the possible side effects of tuberculosis standard therapy?
```
Hepatotoxicity (isoniazid, rifampicin and pyrazinamide)
Peripheral neuropathy (isoniazid)
Optic neuritis (ethambutol)
```
89
Why is there a high likelihood of side effects with tuberculosis treatment?
Because treatment involves 4-9 months of combination therapy
90
Why is antibiotic resistance such a big problem in TB treatment?
The antibiotic treatment takes a long time, meaning that any bacteria left behind will be antibiotic resistant
91
Approximately one-third of the world's population are infected with TB, although many of these cases are subclinical. Why are so many people infected?
Because of the extremely low infective dose - it only takes 1-2 bacilli to infect someone.
92
What is primary tuberculosis?
Initial contact is made by alveolar macrophages and bacilli are taken in lymphatic system to hilar lymph nodes
93
What is latent tuberculosis?
A cell mediated immune response from the T cells, which contains the primary infection but can persist for decades with no clinical signs (although would be detectable on a skin test).
94
What is pulmonary tuberculosis?
Pulmonary tuberculosis occurs as a result of a second infection or immuno compromise - the T cell control of the primary infection can be lost, causing TB to spread throughout the lungs. Granulomas form around the bacilli that settle in the apex of the lungs (these can be necrotic in the centre) and the patient starts coughing up caseous material.
95
Where can TB spread besides the lungs?
It can spread to the CNS and cause TB meningitis (big killer in the AIDS community) and can also spread to the bone and joints.
96
Why are a lot of antibiotics ineffective against TB?
M tuberculosis has a very long generation time, meaning that antibiotics that target cell division are not effective.
97
Why are HIV patients up to 20 times more likely to get TB?
HIV patients often have low CD4 counts. Effective immunity to TB requires CD4 T-cells, which generate interferon gamma and activate intracellular killing by macrophages (mycobacteria have adapted to withstand phagolysosomal killing)
98
How do T-cells contain primary TB infection?
Via the formation of granulomas. The alveolar macrophages take up TB and recruit other immune cells to form granulomas, which can contain the infection. However, if the Th1 response is lost (CD4 depletion, TNFa depletion), granulomas can become unstable and caseous material is released - this commonly happens in elderly individuals have had subclinical TB for a long time.
99
What test can be used to detect latent TB?
Tuberculin skin test (Mantoux test)
100
What are the three groups of worms?
1. Nematodes (roundworms)
2. Trematodes (flatworms, flukes)
3. Cestodes (tapeworms)
101
Why don't adult worms spread from human to human?
They can't reproduce without a period of development outside the body
102
What is the 'pre-patent' period in worm infection?
The interval between acquiring infection and the appearance of eggs/larvae in the stool.
103
How are intestinal nematodes passed from person to person?
Via faecal oral route
104
Loeffler's syndrome causes cough, fever, wheeze and eosinophilia. What causes it?
Infection with Ascaris lumbricoides (large roundworm) - larval migration through the lungs causes Loeffler's syndrome
105
How is Ascaris lumbricoides diagnosed?
Stool microscopy to check for eggs
106
What drugs can be used to treat Ascaris lumbricoides?
Piperazine, pyrantel, mebendazole, levasimole
107
What are the clinical features of hookworm?
Ground itch due to papules at site of entry of the larvae
Pulmonary symptoms
Iron-deficiency anaemia due to adult worms feeding on blood
108
How is hookworm diagnosed?
Stool microscopy for eggs
109
What is the treatment for hookworm?
Iron supplements, pyrantel, mebendazole
110
What is the only common helminth in the UK?
Enterobius vermicularis (pinworm/threadworm)
111
Why does enterobius vermicularis (threadworm) cause pruritis ani?
Because the adult worms live in the large bowel and the female adult emerges from the anus at night to lay eggs on the perineum
112
What are the clinical features of enterobius vermicularis?
```
Pruritus ani
Commonly affects whole families
Appendicitis
Vaginal penetration (can lead to endometritis, salpingitis, infertility)
Occasionally seen in paranasal sinuses
```
113
How can enterobius vermicularis be diagnosed?
Microscopy of a strip of sellotape applied to the perianal region
114
How can enterobius vermicularis be treated?
Using drugs such as mebendazole, piperazine, pyrantel - the whole household should be treated simultaneously.
115
What are the clinical features of whipworm (trichuris trichiura)?
Resident in large bowel
Often asymptomatic
Often co-exists with Ascaris lumbricoides
Trichuriasis results from heavy infestation --> bloody diarrhoea, rectal prolapse, anaemia, wasting, eosinophilia
116
How is trichuris trichiura (whipworm) diagnosed?
Stool microscopy for eggs
117
How is trichuris trichiura (whipworm) treated?
Mebendazole, albendazole
118
Stronglyoides stercoralis causes strongloidiasis. What are the symptoms of strongloidiasis?
Pruritus at the site of larval entry
Pulmonary symptoms due to larval migration
Gut symptoms (malabsorption)
Autoinfection can also occur and in immunocompromised individuals can lead to disseminated strongloidiasis --> diarrhoea, weight loss, malabsorption, paralytic ileus, peritonitis, bacterial infections.
119
Visceral larva migrans is caused by dog and cat roundworms and mainly seen in children. What are the clinical features?
Fever, hepatomegaly, eosinophilia
120
What condition occurs when VLM larvae become trapped in the retina?
Ocular toxicariasis
121
What stomach-wall invading helminth is found in raw fish/crustaceans?
Anisakidae
122
What helminth causes elephantiasis?
Wuchereria bancrofti
123
Blood flukes, liver flukes, lung flukes and bowel flukes all have which organism as an intermediate host?
Snail
124
Katayama fever is present in 50% of patients with which helminth infection?
Schistosomiasis
125
How do humans become infested with Schistosoma helminths?
The miracidium hatches from eggs, infects snail (intermediate host), then cercariae leave snail and penetrate the skin of a human who is in the water. The immature worm enters the bloodstream, lay eggs near the bladder and the eggs enter the intestinal tract or bladder --> passed in urine/faeces
126
What are the 5 major groups of protozoa?
1. Flagellates
2. Amoebae
3. Microsporidia
4. Sporozoa
5. Ciliates
127
What is the more common name for African trypanosomiasis?
Sleeping sickness
128
What causes African trypanosomiasis?
Tsetse fly bite
129
What is the more common name for American Trypanosomiasis?
Chagas disease
130
What organism causes American Trypanosomiasis?
Triatomine bug
131
What are the symptoms of American Trypanosomiasis?
Acute - flu like symptoms
| Chronic - cardiomyopathy, megaoesophagus, megacolon
132
Leishmaniasis is caused by which organism?
Sandfly
133
What are the cutaneous features of leishmaniasis?
Ulceration and tissue destruction
134
What are the visceral features of leishmaniasis?
Fever, weight loss, hepatosplenomegaly, anaemia
135
Trichomonas vaginalis is a sexually transmitted protozoal infection characterised by yellow frothy discharge and dysuria. How is it treated?
Metronidazole
136
How is amoebiasis spread?
Faecal-oral route
137
Amoebiasis can result in dysentry, colitis, and abscesses in the liver/lung. How is it diagnosed?
Trophozoites/cysts can be seen in the stool
138
What is used to treat amoebiasis?
Metronidazole
139
Cryptosporidiosis is caused by a waterborne protozoan. What are the symptoms?
Diarrhoea, vomiting, fever, weight loss, oocytes seen in stool.
140
Cryptosporidiosis is usually self-limiting but can cause severe disease in immunocompromised individuals. If treatment is required, what would be used?
Nitazoxanide
141
Toxoplasmosis is caused by toxoplasma gondii. How would a human contract it?
Ingestion of contaminated food and water or from feline faeces (cats are the only definitive host where full cycle occurs from ingestion to excretion)
142
What severe symptoms can be caused by toxoplasmosis, usually in immunocompromised individuals?
Toxoplasma encephalitis
Chorioretinitis
Disseminated disease
Can also cause congenital toxoplasmosis (microcephaly, hydrocephalus, IUGR, miscarriage) if acute infection occurs during first trimester of pregnancy.
143
Malaria is transmitted by what organism?
Female anopheles mosquito
144
Describe how blood films can help diagnose malaria.
Blood sample taken for thick and thin films. A thick film is sensitive but has low resolution and can determine whether or not a person has malaria. A thin film can identify what species of malaria the person has.
Blood films need to be taken on consecutive days to see the whole lifecycle
145
What are the clinical features of malaria?
Fever, chills, headache, myalgia, fatigue, diarrhoea, vomiting, abdominal pain, anaemia, jaundice hepatosplenomegaly, 'black water fever' (haemolysis --> haematuria)
146
Why does the Plasmodium falciparum variant cause the most severe malaria symptoms?
Red blood cells infected with Plasmodium falciparum have proteinaceous knobs on the surface that bind to endothelial cells in the vessels and other red blood cells, which can result in obstruction of blood vessels with consequent hypoxia of tissues and microinfarcts of the brain and lung.
147
Why might epistaxis, abnormal bleeding and worsening anaemia happen as a result of disseminated intravascular coagulation?
Lots of micro clots form, uses up clotting factors so there are less available circulating in the blood.
148
How is complicated malaria treated?
IV artesunate (IV quinine and doxycycline), as well as other supportive measures to treat symptoms e.g. antiepileptics, oxygen, diuretics, ventilation, fluids, dialysis, broad spectrum antibiotics (sepsis), blood transfusion.
149
How is uncomplicated malaria treated?
There are various options including riamet, quinine and doxycycline, oral chlorquine.
150
Describe the humoral response to viral infection.
Humoral = antibody-mediated.
Antibodies can block virus-host cell fusion and may be involved in opsonisation.
IgM enhances the antibody response, activating complement.
Complement plays a role in opsonisation and lysis.
151
Describe the cell-mediated response to viral infection.
- Interferons from Th cells released --> signal neighbouring cells
- (CD4+) or cytotoxic T lymphocytes can kill infected cells directly
152
What causes most of the damage from viral infections?
Inflammation as a result of immune response
153
How can influenza evade the immune response?
By changing its coat antigen
154
How do mumps, measles, EBV, HIV and CMV evade the immune system?
By causing immune suppression, i.e. destroying/altering lymphocytes and/or macrophages
155
What causes the variability in Influenza coat antigen?
Changes in haemagglutinin and neuraminidase surface proteins
156
What causes flu epidemics?
Antigenic drift caused by spontaneous mutations, which occur gradually and result in minor changes in haemagglutinin and neuraminidase.
157
What causes flu pandemics?
Antigenic shift - sudden emergence of new antigen subtype, which is different to that of preceding virus.
158
What are the four types of adhesins that help bacteria bind to mucosal surfaces?
1. Fimbriae and pili filamentous proteins
2. Non-fimbrial proteins
3. Lipid
4. Glycosaminoglycans
159
How do bacteria form biofilms?
Bacteria stick together on a surface by secreting extracellular substances formed from proteins, polysaccharides and DNA
160
How do trypanosomes evade the immune response?
They have different VSG genes, which control surface antigens. By switching which VSG is expressed, they can change their surface antigens.
161
What two diseases are caused by the varicella zoster virus?
1. Chicken pox
| 2. Shingles
162
Why does VZV remain in a human host lifelong?
The virus core mimics human DNA
163
How does a chicken pox rash evolve?
1. Macule (blob)
2. Papule (palpable)
3. Vesicle (blister)
4. Pustule (pus-filled)
5. Crust
164
How is the chicken pox rash distributed?
Centrifugally - the peripheries are spared because the virus multiples in warm areas of the body
165
How can chicken pox be differentiated from smallpox?
- Smallpox lesions are larger
- Smallpox lesions all evolve simultaneously, whereas chicken pox lesions can be seen at various different stages.
- Smallpox virus divides in cooler areas of the body --> different distribution
- Smallpox affects deeper layers of the skin
166
What are the possible complications of chicken pox?
```
Dehydration
Haemorrhagic change
Cerebellar ataxia
Encephalitis
Varicella pneumonia
Skin and soft tissue infection
Congenital varicella syndrome (pregnant women)
```
167
Chickenpox pneumonitis is the most common complication in adults and affects 15% of healthy adults. How is it treated?
Antiviral treatment: IV acyclovir, then switch to oral valacyclovir when patient starts to improve.
168
Why does shingles normally present as a unilateral rash?
VZV usually lies dormant in the dorsal root/cerebral ganglion. Reactivation causes it to migrate back along the sensory nerve, where it will affect that particular dermatome.
169
What clinical sign indicates corneal involvement of shingles?
Hutchinson's sign - lesion on the end of the nose
170
What can be used to treat pain from shingles?
Gabapentin
171
What would indicate that the immune system is not coping well with shingles?
Shingles lesions appearing in peripheral areas
172
What virus causes hand, foot and mouth?
Enterovirus
173
How does parvovirus cause anaemia?
Human parvovirus targets immature red cells in the bone marrow, attaches to the P antigen and prevents RBC maturation so as the RBCs die, they cannot be replaced.
174
How can parvovirus affect a fetus?
The fetus becomes anaemic, the heart tries to work harder, results in high output cardiac failure and subsequent hydrops fetalis
175
How can hydrops fetalis be detected and treated?
It can be detected by checking blood flow speed on ultrasound and treated with intrauterine transfusion
176
Where are Herpes virus 1 and 2 lesions found?
Herpes 1 - usually the lips, can also appear on the genitals
| Herpes 2 - usually only found on the genitals
177
Which virus causes similar symptoms to glandular fever, is common in teens and young adults and causes swollen lymph nodes and atypical lymphocytes?
Primary cytomegalovirus
178
What are the main symptoms of CMV reactivation?
Retinitis
| Pneumonitis
179
What is the treatment for secondary CMV?
Gancyclovir (or valgancyclovir, which can be taken orally)
180
Describe the rash associated with measles infection
Dry, buttock-sparing, lesions in mucosa look like salt grains
181
Besides a rash, what other symptoms are associated with measles?
Cough, coryza, diarrhoea and conjunctivitis
182
What is an 'enveloped' virus?
One which has a lipid membrane derived from the host cell (e.g. influenza and HIV)
183
What are the main differences between bacteria and viruses?
- Viruses have no cell wall or organelles
- Viruses can have either DNA or RNA, not both
- Viruses cannot replicate outside of a host cell
184
Briefly describe how viruses replicate
1. Attachment to specific receptor on host cell
2. Enter cell via endocytosis
3. Uses host material to transcribe genome to mRNA and translate to proteins, using host ribosomes and nucleotides to either replicate itself or to produce the proteins it needs
4. Assembles itself into a virion once it has what it needs
5. Releases new virus particles - either bursts out of cell causing cell death or in some cases can escape cell via exocytosis, leaving host cell alive
185
Name 5 ways in which viruses cause disease
1. Direct destruction of host cells
2. Modification of host cell
3. Causing 'over-reactivity' of the immune system
4. Damage through cell proliferation
5. Evasion of host defences
186
How does polio virus cause paralysis?
By direct destruction of host cells. It targets neurons, replicates inside them and causes cell lysis and death
187
How does rotavirus cause profuse diarrhoea?
By modification of host cells - it atrophies villi and flattens epithelial cells, decreasing the small intestine surface area, preventing absorption of nutrients and water.
188
How does hepatitis B destroy the liver?
By causing over-reactivity of the immune system. The infected hepatocyte presents the virus antigen, which is recognised by a CTL, which then destroys the hepatocyte.
189
What does the influenza haemagglutinin surface antigen do?
It acts as a 'grappling hook', helping the virus to bind and enter cells
190
What does the influenza neuraminidase surface antigen do?
It acts as 'bolt cutters', cutting the newly formed virus loose from infected cells (leaving host cells alive)
191
Which H and N antigen subtypes have been detected in humans?
H1-3 and N1-2
192
What are the three targets for antibiotics?
1. Cell wall synthesis
2. Nucleic acid synthesis
3. Protein synthesis
193
How do beta-lactams destroy bacteria?
- Bind covalently and irreversibly to penicillin binding proteins
- Disrupts peptidoglycan production
- Disrupts the cell wall
- Causes cell lysis
194
Why are beta-lactams more effective against gram positive bacteria than gram negative?
Gram positive bacteria have more peptidoglycan in their cell walls.
Gram negative organisms have an additional LPS layer that decreases antibiotic penetration
195
Name 3 antibiotics that inhibit nucleic acid synthesis
Rifampicin
Metronidazole
Ciprofloxacin
196
Name 4 types of antibiotic that inhibit protein synthesis
1. Aminoglycosides (gentamycin)
2. Tetracyclines (doxycycline)
3. Lincosamides (clindamycin)
4. Macrolides (erythromycin, clarithromycin, azithromycin, chloramphenicol)
197
Name an antibiotic that inhibits folate synthesis
Trimethoprim
198
Bactericidal antibiotics (e.g. those that inhibit cell wall synthesis) can kill >99.9% of bacteria in 18-24 hours. In which situations are they particularly useful?
- Poor penetration (difficult to get the agent to the bacteria, e.g. endocarditis)
- Infection needs to e eradicated quickly (e.g. meningitis)
199
What do bacteriostatic (i.e. those that inhibit protein synthesis/DNA replication) antibiotics do?
Prevent bacterial replication
200
What is the minimum inhibitory concentration of an antibiotic?
The minimum amount required to prevent microbial growth
201
Antibacterial effectiveness depends on concentration and the time that the antibiotic remains on the binding sites. What are the key parameters in time-dependent killing and concentration-dependent killing?
Time dependent killing - time that serum concentration remains above MCI during the dosing interval
Concentration-dependent killing - how high the concentration is above the MIC
202
Give 4 ways in which bacteria resist antibiotics
1. Changing antibiotic target
2. Destroying antibiotic
3. Preventing antibiotic access
4. Removing antibiotic from bacteria
203
Why is MRSA resistant to flucloxacillin?
Alteration in binding site caused by change in protein folding means that flucloxacillin can no longer bind to that particular type of Staph aureus
204
Why is VRE resistant to vancomycin?
The cell wall components in the enterococci have been changed such that vancomycin binding is reduced
205
How has penicillin resistance arisen?
Some bacteria started to produce beta lactamase enzyme, which hydrolyses the beta lactam ring in penicillins and cephalosporins, meaning that the beta lactams would be unable to bind to the target protein
206
How can bacteria become resistant by preventing antibiotic access?
By modifying bacterial membrane porin channel size, numbers and selectivity
207
Give two ways in which bacteria can acquire resistance to an antibiotic
1. Spontaneous gene mutation
| 2. Horizontal gene transfer
208
Why is metronidazole no use against aerobic bacteria?
Aerobic bacteria are unable to reduce metronidazole to its active form
209
Why is vancomycin no use against gram negative bacteria?
It cannot penetrate the outer membrane
210
Why were carbapenems invented?
They are resistant to degradation by beta lactamases or cephalosporinases
211
What class of bacteria are resistant to carbapenems?
Carbapenem Resistant Enterobacteriaceae - produce 'carbapenemases'
212
How do CRE infections arise?
When people are concentrated with use of antibiotics (e.g. on a hospital ward) and there is a susceptible person
213
What bacteria would be treated with beta lactams?
Susceptible gram positive bacteria
214
When would you use cephalosporins instead of beta lactams?
If the patient has a penicillin allergy
Works against some penicillin resistant bacteria
If the antibiotic needs to reach the CNS, e.g. meningitis
215
What is oral penicillin V good for?
Bacterial tonsillitis - group A/C/G strep. These are currently not resistant to penicillin
216
What antibiotics would you use to treat a Strep pneumoniae infection?
Oral amoxicillin
| IV benzylpenicillin
217
Why would you use flucloxacillin to treat a Staph aureus infection? (not MRSA)
Most Staph aureus breaks down benzyl penicillin
218
MRSA is resistant to flucloxacillin. What would you use to treat it?
Vancomycin and Teicoplanin (IV)
219
When would you use macrolides such as clarithromycin and erythromycin?
In gram positive infections such as Staph aureus and beta haemolytic strep and atypical pneumonia pathogens
Patients with penicillin allergy
Severe pneumonia acquired in the community
220
When would you use lincosamides such as clindamycin?
Gram positive bacteria e.g. Staph aureus, beta haemolytic strep, anaerobes
In cellulitis if the patient has a penicillin
In necrotising fasciitis - clindamycin turns off the toxins produced by gram positive bacteria
221
When would you use doxycycline?
Can only be given orally. Broad spectrum, but mainly gram positive
Can use for cellulitis if the patient has a penicillin allergy
Can be used for pneumonia
222
Gentamicin (IV only) can be used to treat gram negative bacteria, UTIs and endocarditis (synergistically). Why does it require therapeutic drug monitoring?
Due to possible toxic effects (nephrotoxicity and ototoxicity)
223
What can ciprofloxacin be used to treat?
Much more effective against gram negative than gram positive bacteria.
Can be used in patients with penicillin allergies
UTIs
Intra-abdominal infections
224
What is the first line treatment for lower UTIs?
Nitrofurantoin
225
Name two antibiotic treatments with beta lactamase inhibitors
1. Amoxicillin-clavulanate (Co-amoxiclav/Augmentin)
| 2. Piperacillin-tazobactam (Tazocin)
226
What IV antibiotic is effective against both gram positive and negative bacteria and is sometimes used in surgical prophylaxis?
Cefuroxime
227
When would you use meropenem?
In very sick, immunocompromised patients, particularly with HAI
228
What are fungi?
Eukaryotic organisms with a chitinous cell wall, which exist in yeast/mould
229
Why do candida sometimes cause line infections?
They produce a biofilm and are able to bind to plastic
230
What fungal infection is a common cause of meningitis with HIV?
Cryptococcosis
231
What is a non-specific test for fungal infection?
1,3 beta-D glucan - cell wall component of many fungi
232
What are the possible target sites for antifungal drugs?
DNA/RNA synthesis
Protein synthesis
Cell wall (mannoproteins, B1,3-glucan, B1,6-glucan, chitin)
Plasma membrane (contains ergesterol instead of cholesterol)
233
How do polyenes such as amphotericin and nystatin work?
They bind to ergosterol in the fungal cell membrane, intercalate themselves into the membrane and form pores that allow cations to leak out of the cell, causing cell death
234
How do azoles, allyamines and morpholones work?
They inhibit ergesterol synthesis
235
What are clotrimazole and fluconazole effective against?
Candida
| Fluconazole also effective against Cryptococcus
236
What is a normal CD4 count?
>500
237
What is a really bad CD4 count?
<200
238
Why do STIs increase the likelihood of both acquiring and transmitting HIV?
Due to local inflammation
239
What is TasP?
Treatment as Prevention - if an undetectable viral load is maintained, HIV becomes untransmittable
240
What is PEP?
Post-exposure prophylaxis - antiretroviral treatment to be taken for a month, started within 72 hours of exposure
241
What is PrEP?
Pre-exposure prophylaxis, reduces chance of acquiring HIV by ~86%
242
What symptoms are suspicious for HIV?
```
Generalised lymphadenopathy
Acute generalised rash
Glandular fever/flu like illnesses
Oral candida
Unexplained weight loss/night sweats
Persistent diarrhoea
Shortness of breath
Dry cough
Recurrent bacterial infections (inc pneumococcal pneumonia)
Multi-dermatomal shingles
```
243
HIV-1 is a lentivirus and a member of the retrovirus family. What does that mean?
Lentivirus - long incubation period
| Retrovirus - uses reverse transcriptase to make a DNA copy
244
How does HIV invade CD4+ T cells?
HIV has a very high affinity for the CD4 glycoprotein expressed on T cells. It therefore binds to CD4 and is taken into the cell, where it can convert its viral RNA into viral DNA, which is taken up into the cell nucleus.
245
1% of caucasians are homozygous for deletion of which gene which confers some resistance to HIV?
CCR5
246
Why is HIV able to evolve rapidly?
1. Error-prone replication (reverse transcriptase enzyme makes at least 1 error in every replication cycle)
2. Rapid viral replication
3. Large population sizes
247
What are the main symptoms of acute HIV-1 infection?
Glandular fever-like illness (fever, lymphadenopathy, sore throat, oral ulcers, skin rash in upper trunk) - occurs in 90% of people around 3 weeks following transmission
248
What is the natural history of HIV-1 infection?
A high viral load early in infection followed by an asymptomatic period, after which viral load increases again, CD4 level drops, AIDS develops --> death
249
How can HIV evade antibodies in the blood?
- By passing directly from cell to cell, becoming inaccessible to antibodies
- By deriving its virion surface from the host cell membrane
- Heavy glycosylation of the envelope spike makes it difficult for antibodies to bind
250
Briefly explain how immune activation drives HIV pathogenesis
Early in HIV infection, there is a dramatic loss of CD4+ T cells in the lymphoid tissue in the gut. This makes the gut mucosa 'leaky', allowing passage of bacteria and things like LPS, stimulating immune cells and setting up a cycle of chronic immune activation that ultimately exhausts the immune system.
251
What does the HIV-1 nef gene do?
Reduces cell surface expression of HLA class I molecules, which are needed for CTL recognition and also upregulates the death receptor Fas ligand, which can kill virus-specific CTLs
252
What are the diagnostic criteria for AIDS?
When CD4 <200 or an 'AIDS defining illness' is present
253
What is the most common AIDS defining illness?
Pneumocystitis pneumonia (PCP), caused by pneumocystitis jirovecii fungus
254
How is PCP treated?
Co-trimoxazole (+/- prednisolone if the patient is hypoxic)
255
Name 7 AIDS defining illnesses besides PCP
1. Tuberculosis
2. Candidiasis
3. CMV pneumonitis
4. HSV pneumonitis
5. Kaposi's sarcoma
6. Lymphoma (esp primary CNS lymphoma)
7. Toxoplasmosis
8. Cryptococcus neoformans (meningitis)
256
CNS toxoplasmosis is caused by reactivation of latent infection acquired from cat or contaminated meat/water. It causes inflammation at the back of the eye. How is it treated?
Sulphadiazine and pyrimethamine with folic acid
257
Why is HIV associated with Kaposi's sarcoma, lymphomas, cervical/anal/penile carcinoma and hepatocellular carcinoma?
Because these cancers are all associated with viral infections - Kaposi's (HHV8), lymphomas (EBV), cervical/anal/penile (HPV), hepatocellular (Hep B/C)
258
What is HAART and how does it work?
Highly Active Anti-Retroviral Therapy uses at least 3 antiretroviral drugs to target different things - they act on different points in the replication cycle to suppress viral replication.
259
What are the 5 types of drugs used in HAART?
1. Entry inhibitors
2. NRTIs (nucleoside reverse transcriptase inhibitors)
3. NNRTIs (non-nucleoside reverse transcriptase inhibitors)
4. Integrase inhibitors -gravir
5. Protease inhibitors (block HIV proteases to stop HIV from becoming a mature virion) -navir
