Stephen S. Arnon

Honey and other environmental risk factors for infant botulism

Infant botulism results from the in vivo production of toxin by Clostridium botulinum after it has colonized the infants gut. Epidemiologic and laboratory investigations of this recently recognized disease were undertaken to identify risk factors and routes by which C. botulinum spores might reach susceptible infants. Clostridium botulinum organisms, but no preformed toxin, were identified in six different honey specimens fed to three California patients with infant botulism, as well as from 10% (9/90) of honey specimens studied. By food exposure history, honey was significantly associated with type B infant botulism (P = 0.005). In California, 29.2% (12/41) of hospitalized patients had been fed honey prior to onset of constipation; worldwide, honey exposure occurred in 34.7% (28/75) of hospitalized cases. Of all food items tested, only honey contained C. botulinum organisms. On household vacuum cleaner dust specimens and five soil specimens (three from case homes, two from control homes) contained Clostridium botulinum. The known ubiquitous distribution of C. botulinum implies that exposure to its spores is universal and that host factors contribute importantly to the pathogenesis of infant botulism. However, honey is now an identified and avoidable source of C. botulinum spores, and it therefore should not be fed to infants.

Protective role of human milk against sudden death from infant botulism

We examined the possibility that human milk and formula milk might differentially affect the severity of the infant botulism because they differ in immunologic composition and in influence on the normal intestinal microflora against which Clostridium botulinum must compete. A beneficial effect of human milk was suggested by the different feeding experiences of the moderate, hospitalized patients and the sudden death cases. Of patients hospitalized in California, 66% (33/50) were still being nursed at onset of illness, a percentage significantly greater than that of matched controls (P less than 0.01). In contrast, all ten California cases of sudden infant death attributable to C. botulinum infection were being fed iron-supplemented formula milk at death) unlike their controls, P less than 0.02) and had received no human milk within ten weeks of death. A beneficial effect of human milk was also observed in differences in mean age at onset; hospitalized breast-fed patients were almost twice as old (13.8 +/- 6.7 weeks) as were hospitalized formula-fed patients (7.6 +/- 2.9 weeks) (P less than 0.01). Human milk (or possibly other factors associated with breast-feeding) appeared to have moderated the severity at onset of infant botulism, allowing time for hospital admission, whereas for some infants with this illness, formula milk (or possibly other factors associated with formula feeding) was linked to sudden unexpected death.

Clinical Trial of Human Botulism Immune Globulin

A major theme of this conference is that botulinum toxin, nature’s most poisonous poison,1 has now been “tamed” and has acquired the distinction of becoming, through the work of Scott2 and Schantz,3 the first bacterial toxin to serve as a medicine for the betterment of humanity. So in this historic and felicitous context, it appears to be my unwelcome responsibility to remind this conference that botulinum toxin remains very much an adversary for certain select groups of patients, most notably, infants.4

Human Tetanus and Human Botulism

Publisher Summary This chapter describes clinical and epidemiological features of human tetanus and human botulism, the paralytic diseases caused by these most poisonous poisons. Brief mention is made of botulinum toxins use as a therapeutic agent to produce muscle relaxation in a variety of clinical situations. In contrast, at least one malevolent government is known to have recently mass-produced approximately 1,90,001 of botulinum toxin, of which approximately 1,00,001 was incorporated into artillery shells and SCUD missiles. Botulinum and tetanus toxins share the dubious distinction of being the most poisonous substances known; the potency of tetanus toxin is exceeded only by the potency of botulinum toxin. Both toxins exist as simple bi-chain proteins, whose larger component contains the cellular binding site and whose smaller component is a Zn2+-containing endoprotease. The enzymatic light chain cleaves one of three components of the “docking” or “fusion” complex by which the synaptic vesicle fuses with the terminal cell membrane and releases its neurotransmitter. Both diseases originate from one of eight clostridial neurotoxins whose remarkable similarities of structure and mechanism indicate a common ancestral gene, yet the principal manifestations of the two diseases—spastic paralysis for tetanus and flaccid paralysis for botulism—paradoxically represent polar opposites of clinical immobility.

Epidemiological Aspects of Infant Botulism in California, 1976–1991

Infant botulism is the most common form of human botulism in the United States and is now known to be global in extent. The disease, an infectious intestinal form of botulism, was first recognized as a distinct medical entity in late 1976 in California, where all suspected cases are diagnosed microbiologically in this laboratory. Although its clinical spectrum ranges from mild outpatient illness to sudden unexpected death, most recognized cases are hospitalized.