Clinical Management and Sampling

Clinical Management of Cases

Misdiagnosis and differential diagnoses

Misdiagnosis of botulism is not uncommon as botulism is often low on the list of differential diagnoses at presentation. The most frequent misdiagnoses and their distinguishing features are:

     Polyradiculoneuropathy (Guillain-Barre or Miller-Fisher syndrome): antecedent febrile illness, paresthesias, paralysis is often ascending, early loss of reflexes, increased protein in CSF (may not be seen early in illness), typical EMG (electromyography) findings.

     Myasthenia gravis: recurrent paralysis, sustained response to anti-cholinesterase therapy, supportive EMG findings.

     Stroke: often asymmetric paralysis, abnormal CNS image (MRI or CT).

     Intoxication (eg. carbon monoxide, organophosphates, mushrooms): drug detected in body fluids.

Other misdiagnoses and their distinguishing features include:

• Tick paralysis: parasthesias, ascending paralysis, tick attached to skin.
• Poliomyelitis: antecedent febrile illness, asymmetric paralysis, CSF changes.
• CNS infections: changed mental status, changed CSF and EEG.
• Viral syndrome: no bulbar palsies and no flaccid paralysis.
• Psychiatric illness: EMG findings.
• Paralytic shellfish poisoning: onset of paresthesia, food history

Several clinical tests are useful for distinguishing botulism from other diseases, but they may give misleading results:

• Deep tendon reflexes: may be present initially in botulism but decrease or disappear over the following days
• Tensilon tests: negative in botulism but can be transiently positive
• EMG: can be normal early in botulism

Confirmation of the clinical diagnosis

Confirmation is by the detection of botulinum toxin or the bacterium in the patients' faeces, stomach contents, or specimens from wounds, and the detection of toxin in serum samples. Routine laboratory tests are not helpful and specimens should therefore be sent immediately to the reference laboratory. For food-borne botulism, toxin can be detected in the serum of >50% of cases if collected within 1 day of onset, but in <25% after 3 days. However, the bacterium will be present in the faeces in >70% of cases within 2 days of onset and >40% after 10 days. For food-borne botulism, detection of toxin in left-over food may support the diagnosis.

Diagnostic samples

Precautions for sampling

The samples outlined below should be taken to confirm the diagnosis. Standard Universal Precautions (gloves, gowns and hand washing) provide sufficient protection for healthcare workers attending patients and laboratory staff handling specimens. See also; Procedures for transporting samples to the laboratory. The receiving laboratory should be telephoned to expect arrival. Chain of evidence documentation should also accompany all specimens: however in larger incidents this may only be required for the initial cases.

Samples from acutely ill humans to be sent to the National Reference Laboratory

     Serum. At least 10ml serum samples must be collected before antitoxin is administered. Do not send clotted blood.

     Faeces. At least 10g in a sterile container. A portion of the faecal sample (pea size) should be placed in cooked meat medium and sent together with the remaining sample to the Reference Laboratory. This assists detection and isolation of C. botulinum. Rectal washout may be required, since patients with food-borne botulism may have diarrhoea in the early stages, but this is followed by constipation.

     Vomitus, gastric washings or gut contents. At least 10g in a sterile container.

     Bronchiolar lavage or similar in a sterile container.

     Wound. All available pus should be collected in a sterile container and transferred as soon as possible to an anaerobic transport medium. If pus is not available, a swab of the lesion should be taken and put immediately into a transport medium for anaerobic culture. If surgical debridement is performed, biopsy tissues should be placed immediately into a sterile container, then transferred as soon as possible to an anaerobic transport medium.

Other samples

     Post mortem specimens. Heart blood (10ml), if not haemolysed, should be separated into serum before dispatch to the reference laboratory. Specimens of faeces, stomach contents and from infected wounds may also be useful.

     Food samples associated with suspect cases must be obtained as a matter of extreme urgency in order to prevent further cases. The local CCDC or the HPA CfI on-call duty doctor (0208 200 6868/ 4400) should be contacted to arrange collection and transport to the reference laboratory by Environmental Health Departments or other agencies.

     Water: If water is suspected as the source of illness, the HPA CfI on-call duty doctor (0208 200 6868/ 4400) should be contacted to activate the Drinking Water Inspectorate emergency plans and arrange for testing of water samples.

Treatment

Specialist advice should be obtained from an Infectious Disease Physician.

Adults (food- borne or aerosol)

Specific treatment is with antitoxin (see below for source). Antitoxin is held at different sites across the UK and must be accessed by contacting the duty doctor at HPA CfI (0208 200 6868/ 4400; 24 hour service). Detailed instructions on administration are provided with each dose. Antimicrobial therapy is not appropriate.

The antitoxin must be given as early as possible after a clinical diagnosis has been made, and not delayed for the results of confirmatory laboratory tests. The risk of serum sickness or anaphylaxis is very low and a test dose or sensitivity testing is only necessary if there is a known history of allergy to sheep protein.

An effective treatment will prevent further progression of symtoms, but will not reverse established paralysis. Repeat doses are only necessary if the patient continues to deteriorate. The antitoxin dose may be repeated within 24 hours. A repeat dose given within 24-36 hours is most unlikely to cause a severe adverse reaction. Exceptionally a third dose (second repeat dose) may be given within 48 hours if the clinician felt that repeated doses were giving clinical benefit.

It is possible that there may be a late deterioration 2 or more days after an apparently successful treatment. If this occurs within 3 days of onset, further doses may be given, but the chances of an allergic reaction are higher and the patients should be closely observed for signs of anaphylaxis and serum sickness.

Wound botulism

The treatment for wound botulism differs in a number of ways from food-borne and intestinal colonisation:

     Surgical treatment is essential to eradicate the infected lesions and to stop toxin generation.

     Antibiotics are indicated - use penicillin and metronizadole according to standard dosing regimens.

     Repeat doses of antitoxin may be required with up to two repeat doses given within 48 hours.

Intestinal colonisation (infant botulism)

Intestinal colonisation occurs very rarely in adults and treatment with antitoxin must be considered on a case by case basis.

In cases of infant botulism C. botulinum colonises the gut for some time. Human derived botulinum immunoglobulin (BabyBIG®) is now available for the specific treatment of infant botulism and was used for the first time in the UK at Great Ormond Street Hospital in 2007. The treatment is only available from the Infant Botulism Treatment and Prevention Programme (IBTPP) http://www.infantbotulism.org/. Suppotive treatment is important and although paralysis may persist for several weeks, full recovery may be expected as infants recover because they grow new nerve endings.  Excellent advice is available on the infant botulism website given above or advice may be obtained from a paediatrician from a centre that has managed a case.

Antitoxin supplies

Antitoxin is held at sites around the UK - details are available from the duty doctor at HPA CfI (0208 200 6868/ 4400; 24 hour service).

Antitoxin for infant botulism (BabyBIG®) is available from the IBTPP California USA (510)231-7600 for further details: http://www.infantbotulism.org/. 

In a major incident information on how to access stocks of botulinum antitoxin can be found on the DH website.

Infection Control Practice

Decontamination of exposed persons

Botulinum toxin naturally loses activity over a few days, and the toxin does not enter the body through intact skin. An incident specific risk assessment will be required.

The risk of infection from contaminated clothing is low. However, in the event of release of large amounts of toxin, clothing and other fomites may be sufficiently contaminated to pose a risk from hand-to-mouth ingestion. In such situations, decontamination may require:

• Removal of contaminated clothing and possessions – these should be stored in labelled double plastic bags until they can be washed with soap and water.
• Minimal handling of clothing and fomites to avoid agitation.
• Instructing exposed persons to shower thoroughly with soap and water- appropriate facilities will be provided at the scene as necessary.
• Instructing attending personnel to wear appropriate barrier protection – Universal Precautions - when handling contaminated clothing and other fomites.

Isolation of patients

Patient-to-patient transmission of botulism does not occur. Patient room selection should be consistent with availability, but single room placement is not necessary. Universal Precautions are sufficient for the nursing of patients.

Cleaning, disinfection & waste disposal

Standard hospital procedures apply. Contaminated environmental surfaces should be cleaned with hypochlorite solution (5000ppm available chlorine).

Post-Mortem

Autopsy examinations may be carried out with appropriate precautions and the use of standard post-mortem examination personal protective equipment (PPE).

Cremation is the preferred method for disposal of the deceased and embalming is discouraged.

Pacemaker removal is permitted. Pacemaker should be treated with hypochlorite solution (10,000 ppm available chlorine), bagged and disposed of appropriately (not by incineration).

Last reviewed: 23 June 2010