4.1 Toxins (diseases) Flashcards
meningococcal, botulism, tetanus, enterotoxins, cholera, gangrene, necrotising fasciitis, S. pyogenes
Name the bacteria that causes meningococcal disease
neisseria meningitidis
what is meant by gram negative dipolococcus ?
refers to a type of bacteria that appears as pairs of cocci (spherical cells) under a microscope and stains pink or red when subjected to the Gram staining technique.
neisseria meningitidis:
1. aerobic / anaerobic
2. gram staining
3. appearance
4. colonises
- aerobic
- gram negative
- dipolococcus (pairs of cocci)
- nasal cavity
Bacteria causing meningococcal disease (N. meningitidis) …1.. bloodstream or spread ….2… tract
Bacteria release ..3… , triggering the inflammatory response resulting in ..4… and ..5.. necrosis
1 = invade
2 = respiratory
3 = endotoxin
4 = small-vessel thrombosis
5 = skin
What happens after bacteria release endotoxin triggering the inflammatory response in meningococcal disease ?
- small-vessel thrombosis
- skin necrosis
Symptoms of meningococcal disease may include what ?
Family Has V P N
* Fever
* Headache
* Vomiting
* Petechial rash (pinpoint non-blanching points)
* Nausea
What may the sympoms of meningoccocal disease progress rapidly to ?
septic shock , with hypotension, acidosis and disseminated intravascular coagulation
What kind of bacteria is clostridium botulinum ?
Gram staining ? Shape ? Aerobic/anaerobic ? Forms what ?
gram positive, rod shaped, anaerobic, spore forming bacteria
What does clostridium botulinum produce ?
neurotoxin A, B, E, F
List the 4 botulism types that clostridium botulinum is responsible for
- foodborne
- infant
- wound
- adult intestinal
How rare is adult intestinal botulism ?
exceedingly rare
Foodborne botulism happens from what, include an example !
- ingestion of toxin
- improper canned food
infant botulism happens from what, include an example !
- intestinal infection
- consumption of honey
wound botulism happen from what, include an example !
- infection of a wound
- IV drug use
Name a rare and potentially fatal illness caused by toxins produced by C. botulinum
botulism
Symptoms of botulism
weakness, blurred vision, fatigue
What do the symptoms of botulism progress to from weakness, blurred vision, fatigue ?
- muscle weakenss
- effect on cranial nerves -> facial muscle paralysis
- descending paralysis
- effects on autonomic nervous system e.g. dry mouth, postural hypotension
Severe cases of botulism include what symptoms ?
- reduced movement of respiratory muscles
- dyspnea (shortness of breath)
- respiratory failure
Risk factors of botulism ?
- Ingestion of contaminated foods
- infant age group
- travel to the US
- IV drug use
- In the early 1900s what were the commonly source of foodborne illness?
- what are the most common sources of foodborne illness now ?
- commercially tinned foods
- home-preserved vegetables, fruits and fish products
Why is travelling to the US a risk factor of botulism ?
In England and Wales between 1980 and 2013, there were 36 reported cases of foodborne botulism
In the US, there are between 17-43 cases per year
What has would botulism been associated almost exclusively with ?
injection drug users of ‘black tar’ heroin
What is the action of botulinum neurotoxins (BoNT) ?
they block acetylcholine neurotransmitter signal transduction in peripheral α-motor neurons
What are the symptoms associated with usage of BoNT to blockacetylcholine neurotransmitter signal transduction in peripheral α-motor neurons ?
- slurred speech
- peripheral muscle weakness
- paralysis
The action of BoNT (ACh neurotransmitter signal transduciton block in peripheral alpha-motor nuerons) gives it the effect as a clinical therapeutic agent known as ..1… used for ..2.. treatments, …3… and ….4…. treatment
- botox
- cosmetic
- pain management
- migraine
What have iatrogenic botulism cases been reported with ?
therapeutic and unlicensed cosmetic use of botulinum toxin A
How is botulism diagnosed ?
- exclusion of differential diagnosis (guillain barre syndrome, myasthenia gravis, stroke)
- detection of botulinum toxin in blood, faeces, vomit
Treatment of botulism involves what ?
C M V A T
- use of botulinum antitoxin - consist of antibodies against A, B & E
- supportive care
- monitoring of respiratory function
- mechanical ventilation
- surgical treatment of wounds
what is an antitoxin ?
antibody with ability to neutralise a specific toxin
Antitoxins:
1. used on diseases how ?
2. usually used in which method ?
3. example of which immunity ?
- to treat or prevent diseases
- injection
- passive immunity
List features of the clostridium tetani bacteria
(environment bacteria found, shape, gram staining, what it forms, anaerobic/aerobic, motile/not motile)
- common soil bacteria
- rod shaped
- spore-forming gram positive
- anaerobic
- motile with flagella
clostridium tetani responsible = ..1… via ..2… entering the body through a ..3…
- tetanus infection
- spores
- wound
What allows the spores of Clostridium tetani to germinate and grow ? include an example
low oxygen environment
e.g. puncture, contaminated needle injection
Where is bacteria associated with tetanus (clostridium tetani) often found ?
In soil & manure
How does clostridium tetani enter the body ?
- through cuts
- grazes in the skin
- animal bites
- body piercings
- tattoos
- injections
Symptoms for tetanus include ?
SHEPS
* stiffness in jaw muscles
* high temperature
* elevated heart rate
* painful muscle spasms
1. risus sardonicus - spasm of the facial muscles that can resemble a forced smile
2. opsithotonos - body form ‘bridge’ shape backwards
* sweating
What is risus sarcodnicus ?
symptom of tetanus
characteristic grimace or spasm of the facial muscles that can resemble a forced smile
what is opisthotonos ?
symptom of tetanus
a specific posture where the body is rigid and arched backward, with the head and heels bent backward and the body forming a “bridge” shape
What is tetanospasmin ?
tetanus toxin
Where tetanospasmin travel via the bloodstream from wound site too ?
neuromuscular junction of peripheral neurons
What produces the unopposed muscle contraction and spasms in tetanus ?
- tetanospasmin binds to presynaptic membrane of motor neuron and taken up via vesicles into the axon
- interferes with release of neurotransmitters e.g. GABA
- if GABA can’t inhibit the alpha-motor neurons , firing rate increases
What’s the difference between the action of the botulinum toxin and tetanus toxin on neurons ? [is it neurons or muscle cell ?]
- botulinum toxin = blocks release of ACh, stopping muscle contraction
- tetanus toxin = prevents release of glycine and GABA which prevents relaxation of muscles
How is tetanus diagnosed ?
- based on presentation of tetanus symptoms
- spatula test
what is the spatula test as a clinical test to diagnose tetanus ?
touch the posterior pharyngeal wall with a soft-tipped instrument.
If positive, the patient has an involuntary contraction of the jaw and would bite down on the spatula.
Negative test result would be a gag reflex.
Treatment of tetanus includes what ?
- tetanus antitoxin either IV or IM
- Antibiotic therapy (metronidazole)
- benzodiazepines e.g. diazepam to control muscle spasm
Name 3 enterotoxin (type of exotoxin) that cause infectious diarrhoea
- C. jejuni (Campylobacter jejuni)
- Shigella
- E. coli (Escherichia coli)
Name a bacteria that causes of food poisoning ?
Bacillus cereus
Enterotoxin is a type of ..1.. that acts on the …2.. to cause …3..
- exotoxin
- GI tract
- diarrhoea
What are the features of the bacteria vibrio cholerae?
- comma shaped
- highly motile
- gram negative bacteria with a flagellum
What is vibrio cholerae responsible for ?
Infections via ingestion of contaminated water
Cholera = an infection of the ..1.. caused by the ….2.. toxin released by …3..
- small intestine
- cholera
- Vibrio cholerae (V. cholerae)
What does the secretion of the cholera enterotoxin lead to ?
continued activity of adenylate cyclase in intestinal epithelial cells and secretion of water and accompanying salts into the gut lumen
How is cholera spread mostly by ?
unsafe water/food that has been contaminated with human faeces containing the bacteria
Symptoms of cholera ?
Diarrhoea (looks like rice water)- 20 litres a day
Vomiting of clear fluid
Blue-gray skin from loss of fluids
Wrinkled skin
Kussmaul breathing
Cholera is usually a disease of ..1.. affects …2. settings with limited access to ..3.. sources
- poverty
- resource limited
- clean water
Cholera is endemic in how many countries ? mostly which regions ?
- 50
- sub-Saharan
Cholera is described in ..1.. travellers from ..2..
- returning
- Africa / Asia
Highest rates of infection of cholera are in who in endemic regions ?
children under the age of 5
Cholera toxin gains entery to cell how ?
via ganglioside receptor on host epithelial cells
Describe the action of cholera toxin (CT) resulting in severe watery diarrhoea
- CT gains entry to cell via ganglioside receptor
- activates G protein leading to increased adenylate cyclase activity
- ATP -> cAMP, activation of protein kinase
- this leads to ATP mediated efflux of chloride ions via CFTR proteins, leading to loss of chloride ions
- Induces massive fluid secretion in the small intestine
- Inhibition of NaCl absorption inhibits ability of large intestine to reabsorb fluid
Diagnosis of cholera ?
- rapid dipstick test is available to determine the presence of V. cholerae
- stool and swab samples are useful for laboratory diagnosis
Treatment of cholera includes what ?
- use of oral rehydration therapy
- intravenous rehydration with Ringer’s lactate
- antibiotic treatment may be appropriate with doxycyline
Prevention of cholera includes what ?
- water and sanitation measures
- vaccination - oral vaccines available
Vaccination for cholera is not recommended for travellers unless why ?
they have an increased risk of exposure e.g. humanitarian work, or health complications
- What is the exotoxin M protein ?
- also helps with what ?
- A superantigen which is produced by S. pyogenes, which stimulates a systemic immune response
- prevent phagocytosis – tissue invasive exotoxin
- What is the exotoxin alpha-toxin produced by ?
- this causes what ?
- therefore….?
- Clostridium perfringens (an anaerobe)
- excessive platelet aggregation to block blood vessels
- lack of oxygen supply to tissues
2 main types of gangrene ?
- No infection present = dry (ischaemic)
- Infectious = wet/gas gangrene
Infectious (wet/gas gangrene) is often seen what kind of patients ?
- immunocompromised
- diabetic
Infectious (wet/gas gangrene):
1. Infection starts with …?
2. necrotic tissue provides what environment ?
3. what leads to gas production ?
- tissue contamination by bacteria (Group A Strep, Clostridium spp)
- low oxygen environment
- fermentation of glucose
Necrotising fasciitis is what kind of infection ?
bacterial
- What bacteria often cause necrotising fasciitis ?
- bacteria that may be involved in causing necrotising fasciitis ?
- S. aureus, S. pyogenes
- gram negative and anaerobes (C. perfringens)
Mortality from necrotising fasciitis properly treated with ..1.. plus ..2.. has been estimated at between ..3..%.
- surgery
- antibiotics
- 10% and 40
- Mortality is higher in patients who develop … ?
- approaching what percents ?
- shock and end-organ damage
- 50% to 70%
Symptoms of necrotising fasciitis include what ?
- fever
- excessive pain
- red/purple skin from thrombosis
- reduced sensation of the skin
- swelling
Where in the body is necrotising faciitis seen ?
Can occur at any part of the body, but mainly seen at extremities and genitals (Fournier’s gangrene)
Risk factors for necrotising fasciitis ? [how to word for exams ?]
T SAID HI
Trauma
Surgery
Alcohlism
IV drug use
Diabetes mellitus
Herpes zoster (shingles)
Immunosuppression
What type of bacteria is S. pyogenes ?
gram positive cocci that grow in chains
What is S. pyogenes also known as ?
Group A Streptococcus
What is major virulence determinant for S. pyogenes ?
M protein
What can M proteins activate ?
- coagulation
- thrombosis
What do M protein induce production of in monocytes via Toll-like receptors ?
- IL-6
- IL-1 ß
- Tumour necrosis factor - alpha
Diagnosis of necrotising fasciitis involve ?
- elevated white blood cell count
- serum sodium < 135 mmol/L
- raised CRP
- haemoglobin < 11 g/dL
- surgical exploration can also diagnose
Treatment for necrotising fasciitis ?
- surgical wound debridement - to remove necrotic tissue & affected areas
- empirical antibiotics -> broad spectrum to cover gram positive, gram negative and anaerobes
A 34-year-old man presents with the acute onset of blurry vision, nausea, and vomiting. He notes weakness in his arms and trunk. He recently returned from Alaska. Of note, he recalls eating home-preserved fish while visiting a family friend.
1) What investigations would you want to order?
Faecal culture, toxin typing of stool or gastric aspirates.
You’d also want to rule out differentials which can cause paralysis so may want to perform lumbar puncture or electrophysiological testing.
A 34-year-old man presents with the acute onset of blurry vision, nausea, and vomiting. He notes weakness in his arms and trunk. He recently returned from Alaska. Of note, he recalls eating home-preserved fish while visiting a family friend.
‘weakness in arms and legs’ may refer to flaccid paralysis. How does this occur in C. botulinum infection?
Clinical botulism results from the entry of botulinum toxin into the systemic circulation and subsequent inhibition of acetylcholine release from the presynaptic nerve terminal. The toxin enters the circulation through the mucosa (foodborne and inhalational) or via a break in the skin (wound and iatrogenic).
