Journal of the Royal Society of Medicine Volume 84 May 1991 1

A comparison of human and animal botulism: a review

E M R Critchley Do FRcP Department of Neurology, Royal Preston Hospital, PO Box 66, !Sharoe Green
Lane, Preston PR2 4HT

Keywords: botulism; preformed toxin; toxico-infection

Summary C. botulinum appears to have a role at an early

Botulism can arise from preformed toxin, wound stage in the decomposition of animal, and
infection or intestinal toxico-infection. All three forms occasionally vegetable, matter. In anaerobic
can occur in humans as well as in animals. The conditions of increased alkalinity and temperature,
examination of botulism in veterinary practice can spores will germinate with the release of toxin. The
alert the medical profession to the hazards which can various strains of C. botulinum exhibit considerable
occur with the introduction of dietary alterations and poly- morphism and differ widely in colony
hermetic sealing of foodstuffs. There is also the appearance, spore-forming capacity, ability to form
possibility that the development of pica through lack one or more serologically distinct toxins, and in the
of essential nutrients could lead to the ingestion of state of synthesis of the toxin at the time of cell
contaminated substances rendering the child (or even lysis. Thus some toxins are released as fully
adult) susceptible to botulinum intoxication. A activated dichains whereas others require a further
positive gain has been that research leading to process of proteolytic nicking in vivo by intestinal
the elimination of shaker foal disease has provided enzymes to acquire full toxicity°-4. As other bacteria
a comprehensive analysis of factors which may take over, survival of the spores is ensured but the
underline the risk of toxico-infection in infants' 2. toxin is thermo-labile and more rapidly inactivated
as the pH riaes. Nevertheless the greatest
Introduction concentration of spores is to be found in carrion or
The rarity of human botulism contrasts with the spoiled foodstuffs, in larvae, grubs or other
frequent occurrence of animal botulism, involving invertebrates feeding upon carrion, and in soil
tens of thousands of wild fowl each year, herds of underlying carrion.
wild and domesticated animals, and rare species The differences between the serologically distinct
raised in captivitiy. But there are indicators which toxins were exemplified experimentally by Miyazaki
suggest that and Sakaguchi5. Preformed toxins of different types
unless today’s rapid changes in dietary habits, food were administered to 2-week-old chickens intra-
processing and presentation, are matched by increased venously, perorally, and intraduodenally to determine
vigilance into all aspects of food hygiene, food-borne the minimum lethal dose. Intravenously toxin A was
disease, including botulism, may become a more 1000 times more toxic than toxin C. When given
common scourge. Whereas in the past human intraduodenally, toxins C and A were equipotent
botulism was associated with inadequately cleaned, despite the fact that 100 times more toxin C was
salted, smoked or dried fish or meat, the greatest risk absorbed and entered the systemic circulation. In vivo
nowadays arises from commercial or home-prepared production of toxins (toxico-infection) was also
condiments, vegetables, non-acid fruits and preserved examined. The oral administration of 10 C. botulinum
raw fish. Plastic wrapped foods may warm and spores of types A, C or D was aufFicient to kill normal
ferment in anaerobic conditions with survival of toxin 2-week-old chickens. The spores germinated within
at refrigerator temperatures'. the caecum with the production and absorption of
Human disease does not differ fundamentally in toxin. If, however, the caecum was protected by
clinical features, ease of diagnosis, supportive ligation the chickens survived.
laboratory testing, management or therapeutic
measures from that seen in veterinary practice. For Clinical features
these reasons it is proposed to examine the circum- The clinical features of botulism differ little
stances and risk factors which result in outbreaks of between medical and veterinary practice. There are
botulism among animals. excellent accounts of botulism in horses°, cattle',
Cfosfridiurn botulinum is a Gram-positive, lions , foxhounds and baboons' 0 with similar
anaerobic, rod-shaped bacillus widely distributed observations
throughout the world in soil and marine deposits. in aheep and pigs. Descriptions in wildfowl, chickens
Other telluric bacteria, such as C. sporogeneF, and turkey 11 are also surprisingly similar. Animals
present in the same sediments inhibit germination may appear depressed, dull, reluctant to move and
and destroy any toxin produced. Nevertheless, the reluctant to take food. A few may show evidence of
spores can survive for long periods in most dribbling or dropping food from the mouth, abdominal
environmental circumstances, withstanding dry heat distension, a low grade colic or even vomiting. The 0141-0768/91/
but remaining susceptible to acidity, 8-10' o saline disease is not accompanied by fever but is 050295-04/$02.00/0
solutions or moist heat. In its vegetative form the characterized by a flaccid paralysis often starting in the 0 1991
The Royal
organism is an inhabitant of the alimentary canal of hind- quarters with weakness, muBcle tremors,
Society of
herbivores, thereby permitting its carriage to new stumbling and recumbency. The animal may be Medicine
locations. Such forma pose no threat to most adult reluctant to rise, the lying posture may be abnormal
animals. and, on rising, the gait may be stilted and the hind
limbs splayed and
2 Journal of the Royal Society of Medicine Volume 84 May 1991

ataxic. Weakness then progresses to the Most outbreaks among animals are ascribed to
forequarters, head and neck. An abnormal posture infected foods, contaminated foods and unhygienic
of the head may be evident. Apparent lethargy,
conditions' 0""' 8. Modern farming practices may
depression and dullness of expression may be the
also introduce botulism into carcass-free fodder.
result of loss of tone around the eyes and mouth.
Grass harvested for silage is inevitably
The eyes may appear closed, the pupils dilated and
contaminated with soil’. Properly dried big bale
pupillary reflexes sluggish. A diagnostic feature
silage is safe, but if damp, heavily moulded samples
may be the ease with which the tongue can be
are hermetically sealed the pH can be as high as 8.5.
grasped and pulled out of the mouth. Inability to
In an alkaline pH with increasing temperature
swallow may be followed by paralysis of the
spores may germinate with the production of
thoracic muscles and laboured, diaphragmatic
toxin'°.
(abdominal) breathing. When an outbreak occurs
acutely with a very brief incubation period the first Toxieo-infection
evidence may be that a number of horses™'' 3 or Wound infection
baboons' 0 have died for no apparent reason. In Wound botulism, like tetanus, may result from
avian outbreaks of botulism affecting ducks, deep contamination of wounds with the anaerobic
chickens, turkeys, etc. the birds initially appear dull germination of spores within the tissues of the host.
and reluctant to move. The eyes may be closed and Young males with compound fractures are
the necks and wings stretched out with the legs particularly at risk. A comparable example from
tucked beneath them. veterinary practice is provided by Bernard et al.*
who describe botulism as a sequel to open
Preformed toxins castration performed in a barn at a local racetrack.
Death of wildfowl from preformed toxin in shallow Two weeks after surgery, the horse seemed stiff
stagnant water usually occurs in conditions of after galloping and was seen dropping food from its
drought and hot weather. Seepage of water from mouth. It became tremulous, the tone in the eyelids,
alkaline soils and thermal effluence as from power tail, and tongue was markedly diminished, and the
stations' 4 enhance bacterial proliferation where eyelids and tail could be lifted with minimal
there is oxygen depletion. Anaerobic conditions resistance. The tongue could be pulled out of the
develop as the result of an overgrowth of pond side of the mouth and the horse was unable to
weed and the presence of rotting vegetable and swallow. Under anaesthetic the scrotal incisions
organic matter. A subsequent fall in temperature were reopened exposing a neurotic foul-smelling
may allow the toxin to remain stable through the remnant of the spermatic cord. Debridement was
winter months causing further deaths among wild performed and C. t›otufinttm B isolated. Antitoxin
fowl in the following spring' 5. Decomposing and penicillin were given. The horse was fed gruel
carcasses in water are a potent source of via a nasogastric tube. Hydration was monitored
intoxication and many deaths result from pecking at and oral toilet performed. The horse gradually
infected carrion. improved over 10 days’ hospitalization. Drainage
Resistance to the effects of botulinum toxin, either from the surgical site ceased on day 4, muscle tone
innate or acquired, has been demonstrated in some in the tongue and tail improved by day 5, and
carrion-eating mammals and birds. This is not swallowing returned on day 8.
invariably so: foxhounds’ and lions' fed infected meat
may develop botulism. Repeated infections may occur Intestinal infection
in susceptible animals'6; and Greenwood' is convinced Adult toxico-infection ia unusual but has occasionally
that unrecognized mild botulism may occur quite been reported in association with achlorhydria, gastro-
frequently in non-domestic carnivores, particularly if intestinal operations and stagnant loops of bowel.
food hygiene is bad. Because of the extreme potency Infant botulism is well recognized and in many cases
of associated with ingestion of honey which may provide
C. botulinum toxin, it is likely that sub-lethal doaes both the vehicle for the ingress of spores and a non-
are acid environment for their proliferation. Study of the
too small to stimulate an immune response. intestinal micro-flora has suggested that there may
However, with repeated mild infections it is be a delay in the establishment of normal flora, colon-
possible that immunity does develop as is suggested ization by organisms that promote C. botulinum, the
by the presence of antitoxin in carrion-eating birds,
absence of organisms that inhibit C. botulinum, and a
such as the turkey vulture, fish-eating gulls and
crows". Vaccination with C. botulinum toxoid has
been used successfully within herds of botulinum- Table 1. Optimum temperatures for germination and
affected cattle, and to protect racehorses and rare aynthesiz o[toxins. !State o[actiuit y of toxins in uilro
zoological specimens. before absorption and [urther in uiuo activation by
trypsin’"
Destruction of livestock is usually associated with
unnatural necrophagia, eg from the presence of rodent
carcases in fodder' 3. Trout have been infected in fish-
farms after feeding with spoiled marine fish
T'ozins Temperatures State of actiuotion Those aI risk
scraps'6. Lamsieke among cattle in South Africa
develops in times of drought when the parched
A 38-40°C Fully synthesized humans,
grass is deficient in phosphorus. They develop a
animals
craving seeking to replenish the phosphorus from B Nearly fully humans,
the shells of dead tortoises". A similar condition, synthesized animals
called Dry Bible, E 33-35°C Activated by humans,
occurs among sheep and cattle in Western
Australia. Malnourished and undernourished
animals develop
pica and are susceptible to botulism from carrion ' 7. Cannabalism can occur among factory-farmed poultry
 Journal of the Royal Society of Medicine Volume 84 May 1991 3
trypsin animals only
C 1+2 40-42°C Partly activated by trypsin
associated with overcrowding, inadequate trough D Partly activated animals only
space and an unbalanced diet. Failure to remove dead by trypsin
birds may lead to an outbreak of botulism' ®.
change in diet that results in constipation and stasis, toxin is blocked by antitoxin administration. Difficulty in maintaining
allowing the germination and out-growth of spores'". intravenous catheters when affected lions became at all active
Toxico-infection is relatively rare among adult
animals but in one outbreak of type C. botulism in
cattle-fed ensiled poultry litter 20 the outbreak was
biphasic. Preformed toxin accounted for the acute
onset of clinical signs within 72-96 h and the deaths
occurring within 10 days. However, some animals
only became affected about 2 weeks after having had
access to the feed for 24 h. It was concluded that the
ingestion of sublethal amounts of preformed toxin
could serve to debilitate cattle transiently and
possibly act as a prerequisite for in vivo toxin
production from ingested spores.
The prime example of toxico-infection in animals
is provided by shaker foal disease - a neuromuscular
paralytic disease in foals prevalent in Central
Kentucky. In 1967, McQuillen and Cantor confirmed
the presynaptic nature of the neiiro-muscula r block
(unpublished observation) but only later was the
diagnosis of botulism established". The disease most
frequently developed in fast growing foals between
2 and 4 weeks old. At autopsy, neurotic areas were
found in the skin, umbilicus, liver and especially in
the gastric mucosa. It was thought that C. botulinum
spores were ingested from contaminated soil and
faecal material. Whereas in normal circumstances
they are harmless, they are able to proliferate in
necrotic gastric ulcers simulating wound botulism.
Other factors appeared necessary for the disease to
occur. The mares were usually fed on an excessively
nutritious diet and produced an above average
yield of milk with a high fat content. The disease
commonly involved foals after periods of stress to
lactating mares as a result of which the fat content
of the milk contained an excessive amount of
corticosteroids, thereby producing steroid ulcers. This
sequence of events was reproduced and confirmed
experimentally'°.
Toxico-infection usually develops subacutely but
Arnon et al.2’ have questioned whether botulism
may occasionally be responsible for cases of
sudden infant death. The likelihood of thia
possibility is increased by the fact that both
experimentally and in humans cardiac
dysrhythmias and congestive
3
failure can occur with botulism 22'° .

Clinical considerations
The differential diagnosis includes cerebrovascular
accidents, myasthenia gravis and polyradiculopathy,
with the added possibilities of tick paralysis, organo-
phosphate poisoning and adulteration of foods7'°'.
Inter- and intra-species variations in susceptibility to
botulism remain largely unexplained: types C and D
do not cause human disease, and in one outbreak of
type C botulism only male turkeys were affected". A
shared carton of yoghurt caused botulism in two
teen- agers but not their cat°5 and contaminated
chickens fed to lions, jaguars and coatis only
affected the lions .
The principles of treatment are the same in
medical and veterinary practice. With the possible
exception of antitoxin E°°, the efficacy of antitoxins
have not been established. Drugs which enhance
neurotrans- mitter release, eg guanidines and
aminopyridines are short acting and should not be
used in the early stages unless further uptake of
4 Journal of the Royal Society of Medicine Volume 84 May 1991

precluded long-term infusion of neuromuscular junction. Med Biol l98l;58:11-20

3,4-diaminopyridine which might 4 Datta A, DasGupta BR. Botulinum neurotoxin types A,
have led to a more sustained B & E: pH induced difference spectra. 3fof Cell Biochem
reponse . The effects on the 1988;81:187-94
autonomic nervous system have 5 Miyazaki S, Sakaguchi G. Experimental botulism in
not been analysed in animals, but chickens: the cecum as the site of production and
absorption of botulinum toxin. Jpn I Med lsci Biol
there is some evidence of central
1978;31:1-15
nervous system involvement with 6 Bernard W, Divers TJ, Whitlock RH, Measick J,
perivascular haemorrhages in the Tulleners E. Botulism aa a aequel to open castration
corpus striatum, cerebellum and in a hor8e. Am Vet Med Acsoc 1987;10l:73-4
cerebrum°', and of convulsions in 7 Divers TJ, Bartholomew RC, Meaaick JB, Whitlock
seemingly healthy mice after oral RH, Sweeney RW. Clostridium botulinum type B
dosing^. Changes in peripheral toxicosis in a herd of cattle and a group of mules. JAm
nerve conduction25,' have also Vet Med Assoc 1986;188:382-6
been found in 6 dogs found to 8 Greenwood AG. Diagnosis and treatment of botulism in
have food-borne type C lions. Vet ftec 1985;117:58-60
botulism". Blakemore WF, Rees-Evans ET, Wheeler PEG.
Botulism in foxhounds. Yef Rec 1977;98:57-8
10 Lewis ICM, Smith GR, White VJ. An outbreak of
Acbnouiledgments: I am grateful to botulism in captive hamadryas baboons (Papio
Professor M P McQuillen, homadryas). Vet Rec 1990;103:216-17
Department of Neurology, University 11 Smart JL, Laing PW, Winkler CE. Type C botulism in
of Kentucky Medical Center, intensively farmed turkeys. Vet Rec 1983;113:198-200
Lexington, USA, Professor R Jones, 12 Swerczek TW. Toxicoinfective botulism in foals and
University of Liverpool and to adult horaes. Vet Med Assoc 1980;178:217-20
Messrs D Gibbons and R Hogg 13 Ricketta SW, Greet TRC, Glyn PJ, ef nf. Thirteen cases
MAFP, Veterinary Investigation of botulism in horsea fed big bale silage. 'equine Vet ‹f
Centre, Barton Hall, Preston for help 1984;18:515-18
with references. 14 Haagsma J. The etiology and epidemiology of botulism
in waterfowl in the Netherlands. H ydrobiol Bull
References 1973;7:96-105
1 Thatcher P•S, Robinson J, 15 Graham JM, Smith GR, Borland ED, Macdonald JW.
Endman I. The “vacuum pack” Avian botulism in winter and spring and the stability
method of packaging foods in of Clostridium botulinum type C toxin. Vet Rec
relation to the formation of the 1978;102:40-2
botulinum and staphylococcal 16 Smith GR. Botulism in waterfowl. Symposin Too Soc
toxins. Appl Bacteriol Zondon 1982;60:97-119
1962;25:120-4 17 Meyer KF. The status of botulism as a world health
2 Graham JM. Inhibition of problem. Bull World Health Organ 1956;16:281-98
Clostridium botulinum type C 18 Blandford TB, Roberts TA. An outbreak of botulism in
by bacteria isolated from mud. ‹f broiler chickens. Vet Ret 1970;87:258-61
Appl Bacteniol 1978;45:205-11 19 Wilcke BW, Midura TF, Arnon SS. Quantitative
3 Sellin LC. The action of evidence of intestinal colonisation by Clostridium
botulinum in four caaes of infant botulism. Infect Dis
botulinum toxin at the
1980;141:419-23
20 Neill SD, McLoughlin MF, McIlroy SG. Type C Funthen details com: M P Steams, 97 Harley Street,
botulism in cattle being fed ensiled poultry litter. Vet London WIN IDF (Tel: 071-487 4695a
Rec 1989;l24:558-60
First North Sea Meeting on Venous Diseases Fourth Anglo-French
21 Arnon SS, Midura TF, Damus K, Wood RM, Chin J.
Intestinal infection and toxin production by Meeting on Phlebology 30 May-1 June 1991, Amsterdam, The
Clostridium botulinum as one cause of sudden infant Netherlands
death syndrome. L.ancet 1978;i:1273-7 Further details com: Symposium Office, PO Box 39 5720 AA Asten, The
22 Vernant P. Formes cardiaques du botulisme. Ann Netherlands
Microbiol (Inst Pasteur) 1979;130A:141-2 Strengthening Community Capacity to Prevent and Control Disease:
23 Smith GR. Individual variation in botulism. Br I Exp Implementing Treatment and Pre- vention Programs for Children
Pathol 1986;67:617-21 12-14 June 1991, Carter Presidential Centre, Atlanta, Georgia Further details from:
24 Name LA. Selected neurotoxins. Vet Clin North Am INMED, 103 Loudoun Street, SW, PO Box 4200, Leesburg, VA 22075, USA
Small Anim Pract 1988;18:593-604 (Tel: 703 771 0011)
25 Critchley EMR, Hayes PJ, Isaacs PET. Outbreak of
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 Journal of the Royal Society of Medicine Volume 84 May 1991 5
Further details from: Dr Rachel Strachan (Short Courses),
botulism in North West England and Wales. June 1989.
Department of Biological Sciences, University of Warwick,
Lantet 1989;ii:849-53
Coventry CV4 7AL (Tel: 0203 523523 ext. 3540;
Pax: 0203 523701a 26 Larson HE. Botulism. In: Weatherall DJ, Ledingham
JGG, Farrell DA, eds. Oxford textbook o[ medicine,
vol 1. Oxford University Press, 1984:230
27 Smith LDS. Botulism, the organisms, its toxins, the
disease. Springfield, Illinois: CC Thomas, 1979
28 Sonnabend WF, Sonnabend OA, Grundler P, Katz E.
Intestinal toxicoinfection by Clostridium botulinum
type F in an adult. Lancet 1987;i:357-60
29 van Ness •IJ. Botulism and Guillain-Barre syndrome.
Lancet 1987;i:1033

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