Page 787 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

746 SECTION | XI Bacterial and Cyanobacterial Toxins

VetBooks.ir TOXICOKINETICS largely confined to the industrial toxin manufacture. It is
Inhalation botulism: this form is very rare and is
While all aspects of the toxicokinetics may not be rele-
the major route of exposure for weaponized botulinum
vant to specific situations (e.g., oral absorption is not rele-
toxin (Arnon et al., 2001a,b).
vant to wound botulism), a general overview has been
Iatrogenic botulism: this form involves the misuse or
provided (Simpson, 2013).
accidental overdosing of pharmaceutical botulinum toxins.
Absorption: There are two broad pathways of absorption:
Human infant botulism: this is due to anaerobic condi-
oral and parenteral (via wounds). Inhalation exposure is an
tions in the gut that allow for germination of ingested
unusual circumstance that is unlikely to be encountered out-
C. botulinum spores in human infants under 6 months of
side of bioweapon use and toxin manufacturing facilities
age (Brook, 2007). Honey containing C. botulinum spores
Release of botulinum toxins by Clostridia sp. is in the
is a major cause of this disease with up to 20% of honey
form of a noncovalently associated progenitor complex
specimens containing the spores (Nakano et al., 1990).
consisting of hemagglutinins (Has: three different classes,
Adult intestinal toxemia botulism: this occurs when
HA1 3), nontoxic nonhemagglutinins (NTHA: one
the normal gut flora has been altered due to antibiotic
class), and botulinum toxin. Notably, serotypes E and F
therapy or surgical procedures.
do not produce HAs. HAs and NTHA increase the oral
Wound botulism: this occurs with infection of deep
potency of botulinum toxins by decreasing their proteoly-
anaerobic wounds with C. botulinum.
sis in the gut. In particular, NTHA has been described as
essentially acting as a “bioshield.” There is also limited
in vitro evidence that HAs may disrupt enterothelial tight BOTULISM IN VETERINARY SPECIES
junctions, thus facilitating paracellular transport.
Critically, HAs are not essential for intestinal absorption. Equine Botulism
Absorption across relevant epithelia displays the fol-
Horses are amongst the most susceptible species. Equine
lowing features: (1) it is an active, receptor-dependent,
botulism in North America is mostly due to serotype B
endocytosis/transcytosis process that is not dependent on
( . 80% of equine cases) although cases involving sero-
HAs or NTHA; (2) the critical domain for endocytosis/
types A and C1 have been reported (Whitlock, 1996;
transcytosis across epithelia is located is associated with
Johnson et al., 2010). C. botulinum serotype B strains are
the carboxy terminal end of the toxin heavy chain; (3) dif-
ubiquitous in the soils of the northeastern and central
ferent epithelia have different relevant receptors; and (4)
United States (particularly a zone extending from Kentucky
the cellular handling of botulinum toxins by epithelial
to the mid-Atlantic states). Serotype A strains are more
cells is different from what occurs in neurons.
prominent in the western states (California, Utah, Idaho,
Distribution: botulinum toxins essentially distribute to
and Oregon) and in Ohio. Botulinum serotype C1 cases
the non-CNS extracellular fluid compartment. The toxin
have been reported in California, Florida, the New England
obeys a classical 2 compartment model elimination kinetics
states, and Canada.
with a distribution phase and an approximately first-order
Horses acquire botulism in one of three ways: (1)
elimination phase. Botulinum toxins are highly
from the ingestion of preformed toxin in contaminated
stable within the circulation and the general circulation acts
foodstuffs; (2) from anaerobic wound contamination with
as a “holding compartment.” The handling of the toxin with
C. botulinum; and (3) from the colonization of the intesti-
the neuronal compartment has been described above.
nal tract with C. botulinum bacteria (toxicoinfection).
Metabolism and elimination: the metabolism and elim-
The ingestion of preformed toxin in spoiled or
ination of botulinum toxins remains poorly described.
carrion-contaminated foodstuffs is the most common sce-
Critically, the persistence of biologically active toxin
nario. Contaminated feed sources such as alfalfa cubes,
within the general circulation holding compartment likely
alfalfa hay, baled hay, wheat, oats, potatoes, bale silage,
contributes to the severity of the disease.
rye silage, grass clippings, oat chaff, and brewer’s grains
have all been purported sources (Whitlock and Buckley,
1997). Serotype B is more commonly associated with
BOTULISM IN HUMANS
spoiled foodstuffs or moldy hay. Damp, alkaline condi-
Food-borne botulism (Kerner’s disease): the disease is tions in spoiled vegetation are optimal conditions for clos-
due to the ingested of food containing preformed toxin. It tridial growth, sporulation, and toxin production. For
is most common in food preserved under anaerobic condi- these reasons, it is recommended that silage with a pH
tions. While the spores of C. botulinum are heat-resistant, greater than 4.5 should not be fed to horses (Whitlock and
the toxin itself can be destroyed by boiling (WHO, 2013). Buckley, 1997; Galey, 2001). Storage of silage and hay in
A major objective of food preservation is the destruction large plastic bags is a risk factor.
of the toxin and creation of conditions unfavorable to Carrion-contaminated feed is most commonly associ-
clostridial growth. ated with botulinum toxin C1 (Galey, 2001; Kinde et al.,