The Pathophysiology of C. botulinum toxin

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Table of Contents

Anti-Plagiarism Declaration

Introduction

Clostridia: General Characteristics

C.tetani: Tetanus

Symptoms

Cause

Pathophysiology

Diagnosis

Prevention

Treatment

Prognosis

Epidemiology

C.botulinium: Botulism

Symptoms

Cause

Pathophysiology

Diagnosis

Prevention

Treatment

Prognosis

Epidemiology

C. perfringens: Cellulitis and Gas Gangrene

Symptoms

Cause

Pathophysiology

Diagnosis

Prevention

Treatment

Prognosis

Epidemiology

Other Clostridial Diseases

Food Poisoning

Bacteremia

Pseudomembranous Colitis

Non-Spore-Forming Anaerobes

Bibliography

Introduction

Anaerobic bacteria can be classified as bacteria with spores or without spores. All bacteria that belong to the Clostridium genus are spore forming and the stain gram-positive. Non-spore-forming bacteria have a wider variety and they are not completely characterised. These may stain gram-negative/gram-positive. Anaerobic bacteria are problematic as they are generally overlooked during an examination due to the difficulty in isolating and growing them in a pure culture.

Clostridia: General Characteristics

  • Largest spore-forming species of bacteria those are gram-positive
  • With exposure to oxygen, they can die
  • Short life span
  • An active metabolism
  • Can produce a variety of poisonous toxins

C.tetani: Tetanus

Symptoms

  • Headaches
  • Jaw cramping, "lockjaw"
  • High blood pressure
  • Increased heart rate
  • Painful muscle stiffness
  • Not able to swallow properly
  • Seizures
  • Fever
  • Sweating

Cause

Tetanus is caused by lacerations, abrasions, burns, body piercings, any injury to the eyes and being bitten by an animal.

Pathophysiology

Tetanus toxins are very strong that targets proteins. They enter through the spinal cord and affect the synaptic junction. The toxins get in through the neuron terminals and affect the lower motor neurons that control skeletal muscle (voluntary movement). Proteins at the nerve terminal are affected which decreases neurotransmitter release. These effects will first lead to paralysis then muscles spasms.

Diagnosis

There are no medical lab tests that can confirm the presence of tetanus but diagnosis for it is based on the clinical disease. When someone may have tetanus they need:

  • To be hospitalised
  • Get the vaccination
  • They will need treatment with human tetanus immune globulin (TIG)
  • Muscles spasms will need to be controlled with medication
  • Antibiotics will be administered
  • Treatment of the wound

Prevention

  • Vaccination (tetanus toxoid) - should begin from an infant of 6 weeks old
  • Neonatal umbilical cord tetanus can be avoided by immunizing the pregnant female that has not been immunized previously

Treatment

  • Administration of tetanus immune globulin when clinical tetanus is indicated, this is an antitoxin which inactivates the tetanus toxin at the neuronal synapse
  • Wound should be treated by removing any dead/damaged tissue
  • Antibodies are taken to prevent bacterial growth
  • Vaccination (tetanus toxoid) is given to those who have not been immunized for the past 5 years
  • Antispasmodic medication is only administered if muscles spasms have occurred

Prognosis

  • 20-25% of people will die from infection
  • Young children or older people will have more severe cases
  • People older than 65 years old are likely to die
  • The intensity of the symptoms can indicate the severity of the infection
  • Intensive care can help improve serious cases of tetanus
  • The disturbance of heart rhythms and respiration failure is what causes death due to tetanus infections
  • Infant deaths due to neonatal umbilical cord tetanus is at 60-80%

Epidemiology

  • Materials in contact with animal waste
  • Soil
  • Wounds from war (before vaccination)

C.botulinium: Botulism

There are 3 types of botulism: food borne, wound and infant.

Symptoms

Food borne and wound botulism:

  • Unable to speak/swallow
  • Eyelids are droopy
  • Facial weakness
  • Vision is either doubled/blurred
  • Difficult to breath
  • Vomiting, nausea and abdominal cramps
  • Paralysis

Infant botulism:

  • Constipation
  • Drooling
  • Eyelids are droopy
  • They have a weak try
  • The infant will tend to be very irritable
  • Problems with feeding/suckling
  • Tiredness
  • Paralysis
  • Muscle weakness

Cause

  • Food borne botulism: This is caused with contaminated food with relation to infected soil. If the food is not preserved or cooked properly, the C. botulinum bacteria can produce the harmful toxins
  • Wound botulism: This type of botulism is caused by the wound being infected with the bacteria and its cases are mainly drug related (sniffing/injecting)
  • Infant botulism: When an infant ingests the bacteria spores, they become infected with botulism as their immune system is not developed enough to attack the bacteria. The bacterium goes into the digestive system where it will start to produce toxins.
  • Other causes can include drinking water with the toxin; breathing in the toxin when it is in a gas form and incorrect injection of the C.botulinum toxin

Pathophysiology

C.botulinum toxin that enter the body are absorbed by the stomach/small intestines; when the digestive enzymes do not denature then and they then affect the neuromuscular junction. The toxin will affect the release of acetylcholine from the presynaptic cleft of the nerve terminal, leading to the muscle not being active anymore. This leads to paralysis and eventually hypotonia. This effect is evident in several other systems in the body like the endocrine system and nervous system.

Diagnosis

Since the early symptoms of botulism can be confused with those of other diseases, traces of the bacteria need to be found in faeces, serums and gastric washing. The suspected food that may be contaminated will also be tested. It is very hard to recognise the symptoms of botulism even when isolated, so tests on mice are performed to prove its presence.

Prevention

Food should be prepared properly like home-canned foods, as to destroy any spores that may be present. By boiling the food or putting it in a pressure cooker for several minutes, this will decrease chances of getting infected.

Treatment

Antitoxin will be administered when botulism is suspected. The antitoxin will only neutralise the toxins in the body and not heal the affected areas/nerves. In some cases, respiratory support is needed especially in infants.

Prognosis

  • Recovery is prolonged
  • Extensive rehab is needed
  • Respiratory muscles are weak and take approximately a year to function properly but the capacity to exercise is reduced
  • Mortality is approximately 7-10%
  • Over the age of 60, the mortality rate is doubled
  • Patients will complain of tiredness, dry mouth, shortness of breath and weakness

Epidemiology

  • Due to home-canned/preserved foods
  • There are very rare cases of botulism with regard to commercially canned foods

C. perfringens: Cellulitis and Gas Gangrene

Symptoms

Cellulitis:

  • Infected area is painful
  • Inflammation/redness
  • Rash/ skin sore that grows rapidly
  • Swollen appearance of the infected skin
  • Fever
  • Warmth in the infected area
  • Fatigue
  • Muscle pains
  • Sweating

Cause

Cellulitis:

  • When the bacteria can enter through the skin due to cuts, surgical incisions and insect bites

Pathophysiology

Cellulitis:

  • Lymphatic blockage
  • Venous insufficiency

Diagnosis

Cellulitis:

  • Swelling of the skin
  • Drainage of the infected area
  • Swelling of the glands
  • Redness & warmth

Prevention

Wound should be cleaned immediately and antibacterial ointment should be applied. Prevent the skin cracking by keeping it moist; treat superficial infections; wear protective clothing especially when working; inspect feet for any injury.

Treatment

Cellulitis:

  • 2 weeks of oral antibiotics, elevate limb to reduce swelling

Gas Gangrene:

  • Remove dead tissue, if the infection continues to spread it will lead to amputation

Prognosis

Cellulitis:

  • Response to treatment would be within 2-3 days. In rare cases, the patient can become seriously ill. Surgery may be needed and will result in scarring

Epidemiology

  • Age: Facial cellulitis over the age of 50, or children from 6 months to 3 years; Perianal cellulitis mainly affects children
  • Gender: Cellulitis is generally equal except for perianal cellulitis which is more in males than females
  • Geography: mainly found in the coastal regions
  • Socioeconomical status: Immigrants that are not vaccinated against tetanus and Haemophilus influenzaetype b; Overcrowded areas; people working in gardens, farms or sea life have an increased risk.

Other Clostridial Diseases

Food Poisoning

This is caused by the bacterium, C.perfringens. Food poisoning is mainly caused by eating contaminated meat was they can survive the normal cooking temperature and thrive when the meat cools down. Once within the body, the bacteria go into the intestines where they begin to grow and produce its relative toxins. Symptoms of food poisoning are diarrhoea, abdominal pain and cramps. The prognosis of this infection is that it cannot lead to death but can be fatal especially in children

Bacteremia

Bacteremia is when bacteria is in the bloodstream. Cases like this are serious; this condition is associated with specific types of cancer.

Pseudomembranous Colitis

The bacterium, C.difficile is the cause, and can be found in hospitals. It is found in the intestinal tract (in a few cases), but is dominated by the normal bacteria present. When antibiotics are taken, it destroys the normal bacteria and C.difficile is able to take over and produce toxins. The toxins produced cause a collection of fluids and damage of bowel cells. A third of the patients with this condition die as they have to fight against the initial infection and the bacteria.

Non-Spore-Forming Anaerobes

Symptoms

Bibliography

Causes of Botulism (2014), 23 April, [Online], Available: http://www.nhs.uk/Conditions/Botulism/Pages/Causes.aspx [12 July 2014].

Causes of Tetanus (2013), 17 July, [Online], Available: http://www.nhs.uk/Conditions/Tetanus/Pages/Causes.aspx [12 July 2014].

Cellulitis, [Online], Available: https://www.clinicalkey.com/topics/surgery/cellulitis.html#707901 [12 July 2014].

Chan- Tack, M.K.M. (2013) Botulism, 28 May, [Online], Available: http://emedicine.medscape.com/article/213311-overview#aw2aab6b2b2aa [12 July 2014].

Charles Patrick Davis, M.P. (2014) Tetanus (cont.), 30 May, [Online], Available: http://www.emedicinehealth.com/tetanus/page10_em.htm#tetanus_prognosis [12 July 2014].

Hassel, B. (2013) 'Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms', Toxins, vol. 5, no. 10.3390, January, pp. 73-83, Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564069/ [12 July 2014].

Herchline, T.E. (2014) Cellulitis, 1 April, [Online], Available: http://emedicine.medscape.com/article/214222-overview#a0104 [12 July 2014].

Normandin, B. (2012) Cellulitis, 15 August, [Online], Available: http://www.healthline.com/health/cellulitis#Overview1 [12 July 2014].

Staff, M.C. (2012) Botulism , 19 July, [Online], Available: http://www.mayoclinic.org/diseases-conditions/botulism/basics/symptoms/con-20025875 [12 July 2014].

Tetanus (2013), 9 January, [Online], Available: http://www.cdc.gov/tetanus/about/symptoms-complications.html [12 July 2014].

Wenham, T. and Cohen, A. (2008) Botulism, [Online], Available: http://www.medscape.com/viewarticle/574270_5 [12 July 2014].

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