Botulism: a rare complication of injecting drug use

Botulism is a rare, naturally occurring disease that may also be caused by deliberate or accidental exposure to the toxins of Clostridium botulinum. The three types of naturally occurring disease are food-borne, wound and intestinal colonisation botulism, dependent on the route of ingress of the toxins. Food related botulism remains rare in the UK, but wound botulism is increasing, particularly associated with intravenous drug use. It presents with an afebrile, descending, symmetrical, flaccid paralysis of motor and autonomic but not sensory nerves. Respiratory failure can occur rapidly with little prior ventilatory deterioration. Management includes respiratory support, specific antitoxin and surgical debridement and antibiotics for cases of wound botulism. We report a case of wound botulism and discuss the presenting features that should alert the emergency physician to the diagnosis of wound botulism.     

Infectious agents of bioterrorism: a review for emergency physicians

The terrorist attacks on the United States in 2001 and the anthrax release soon after brought the issue of bioterrorism to the forefront in the medical community. Bioterrorism is the use of a biologic weapon to create terror and panic. Biologic weapons, or bioweapons, can be bacteria, fungi, viruses, or biologic toxins. Because the emergency department represents the front line of defense for the recognition of agents of bioterrorism, it is essential that emergency physicians have the ability to quickly diagnose victims of bioterrorism. This review examines the most deadly and virulent category A agents of bioterrorism, that is, anthrax, smallpox, plague, botulism, hemorrhagic fever viruses, and tularemia. The focus is on epidemiology, transmission, clinical manifestations, diagnosis, and treatment.     

Food-borne botulism

Botulism is a neuroparalytic disease caused by neurotoxins produced by Clostridium botulinum, and classically presents as palsies of cranial nerves and acute descending flaccid paralysis. Food-borne botulism is the most common form of botulism, and caused by preformed neurotoxins produced by Clostridium botulinum. Electrophysiological studies play an important role in the early diagnosis. Confirmation of the diagnosis is based on the detection of botulinum toxins in the patient's serum or stool. In Japan, decades ago, botulism type E occurred, though only sporadically, almost every year, but in recent years, has dramatically decreased in frequency. Botulism is a curable disease when treated early and adequately. Differential diagnosis of cranial nerves and limb muscle palsies with rapid exacerbation should include food-borne botulism.     

An Outbreak of Botulinum Types A,B, and E Associated With Vacuum-Packaged Salted Fish and Ham

BackgroundBotulinum toxin is a neurotoxin generated during the growth of Clostridium botulinum and can lead to a rare but life-threatening disease with neurologic symptoms. Relatively little is known about the many types of botulinum toxins in China. The clinical symptoms of the different types of botulism toxin–induced illnesses appear after an incubation period and vary greatly by the serotype and degree of exposure to the toxin.Case ReportWe describe 4 patients who consumed vacuum-packaged salted fish and ham and then presented with severe gastrointestinal symptoms, resulting in vomiting and one death. Blood serum and urine samples tested by the botulinum neurotoxin Endopep-MS assay were positive for botulinum toxin types A, B, and E. The patient who consumed the largest amount of fish and ham died after 36 h, and the other patients were treated with botulism antitoxin after being diagnosed with a botulinum toxin–induced illness and recovered after 1 month. These cases illustrate the importance of early diagnosis and early treatment of botulism type E, in particular, because of the risk of respiratory failure and treatment delays, which can result in increased mortality and poorer overall outcomes.Why Should an Emergency Physician Be Aware of This?Our cases illustrate the importance of early diagnosis and especially the treatment of illnesses related to botulism type E because of the risk of respiratory failure and because treatment delays can result in increased mortality and worsened overall outcomes.     

Botulin toxin: a weapon in terrorism.

Clostridium botulinum, the causative agent of botulism is an anaerobic, spore forming gram-positive bacillus. C. botulinum causes three types of botulism; foodborne botulism, wound botulism, and infant botulism. Most strains of the bacterium produce a potent, muscle-paralyzing neurotoxin. Respiratory failure secondary to paralysis of the respiratory muscles can lead to death unless appropriate therapy is promptly initiated. Due to the severity and potency of this neurotoxin, its importance as a biological weapon is of major concern to public health officials.     

Bacterial toxins with intracellular protease activity

The recent determination of their primary sequence has lead to the discovery of the metallo-proteolytic activity of the bacterial toxins responsible for tetanus, botulism and anthrax. The protease domain of these toxins enters into the cytosol where it displays a zinc-dependent endopeptidase activity of remarkable specificity. Tetanus neurotoxin and botulinum neurotoxins type B, D, F and G cleave VAMP, an integral protein of the neurotransmitter containing synaptic vesicles. Botulinum neurotoxins type A and E cleave SNAP-25, while the type C neurotoxin cleaves both SNAP-25 and syntaxin, two proteins located on the cytosolic face of the presynaptic membrane. Such specific proteolysis leads to an impaired function of the neuroexocytosis machinery with blockade of neurotransmitter release and consequent paralysis. The lethal factor of Bacillus anthracis is specific for the MAPkinase-kinases which are cleaved within their amino terminus. In this case, however, such specific biochemical lesion could not be correlated with the pathogenesis of anthrax. The recently determined sequence of the vacuolating cytotoxin of Helicobacter pylori contains within its amino terminal domain elements related to serine-proteases, but such an activity as well as its cytosolic target remains to be detected.     

Practical strategies against bioterrorism

Bioterrorism is terrorism by intentional release of viruses, bacteria, toxins or other agents to cause illness or death in people. Especially, anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fevers are important illness due to biological agents with a high potential for adverse public health impact. These biological agents can be spread through the air, through water, or in food and may cause disasters in the society. Furthermore, difficulties in detection and identification of the bioterrorism agents may result in immense harm. Then we need to take actions for the preparation for unexpected events to keep the damage to a minimum.     

Botulinum toxin

Botulinum toxin is regarded as the most lethal substance known. It is estimated that the human LD50 for inhalation botulism is 1 to 3 nanograms of toxin/kilogram body mass. Although only three cases of inhalational botulism have been described, an understanding of the pathophysiology of food-borne outbreaks, wound botulism, and infant botulism, and their therapies, enables the medical community to plan treatment in the event of an aerosol release of botulinum toxin. Antitoxin, vaccine, and F(ab')2 immune fragment therapies are discussed as adjuncts to supportive therapy.     

Type E botulism

There are seven known serotypes of botulism, designated A through G; almost all human cases of botulism are caused by types A, B, and E. Botulism type E is the predominant serotype causing disease associated with native Arctic foods. In the circumpolar regions of the world, the coastal soils are rich in botulism type E, and consumption of fish and marine animals in these areas are the sources of clusters of botulism. Unlike spores of type A and B, botulism type E can withstand freezing down to 3.5°C. Alaskan native fermentation of fish heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum toxin to be elaborated from Clostridium botulinum. The consumption of whale meat, “muktuk” has also been associated with outbreaks of botulism in Alaska and the Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been associated with Norwegian “rakfisk” prepared by a process similar to fermented Alaskan foods. Outbreaks in Egypt with the salted gray mullet “faseikh”, in Israel and New York linked to salted uneviscerated whitefish “kapchunka”, in Iran from eating “ashbal” an uncooked salmon, and in Japan with “izushi” a traditional fermented fish preserved in rice have occurred. Importation of vacuum-packed whitefish from Alaska and Canada has also been associated with sporadic cases of botulism type E in Europe. In March 2010, the Center for Disease Control and Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under an Investigational New Drug program, as the preferred treatment for food-borne botulism, including type E, which had not been covered by the bivalent antitoxin, the prior approved antitoxin product in the USA.     

Wound botulism associated with black tar heroin and lower extremity cellulitis

Wound botulism is a rare and potentially fatal disease. The use of black tar heroin has spawned an increase in the incidence of the disease, with the majority of cases occurring in California. The use of botulism antitoxin and surgical debridement are recommended to decrease hospital stay. For this to be effective, the diagnosis of wound botulism first must be considered, followed by an aggressive search for any area of infection that may be debrided. This case report demonstrates several factors to consider in patients presenting with symptoms of botulism poisoning: occurrence away from the Mexico border, no obvious abscess, and the need for prolonged ventilatory support. This case report documents a prolonged hospital stay, possibly caused by delay in administration of antitoxin in a patient with cellulitis that was not considered appropriate for debridement.     

Botulisme: pas toujours une intoxication par ingestion

Botulism is a rare but paralyzing disease caused by a neurotoxin produced by the anaerobic, spore-forming Gram-positive bacterium. Clostridium botulinum. Temperatures of over 120° C are required to kill the spores, while a one-minute exposure to 85° C is sufficient to inactivate the toxin. Although in most cases botulism is caused by eating contaminated food, experimental data and documented cases of botulism in laboratory workers clearly indicate that an aerosolized form of the toxin may also provoke botulism, i.e., that the bacterium can be inhaled. Moreover, according to experts, the use of aerosolized botullinum toxin could be one of the most frightening weapons in the context of biological warfare. We report one case of documented botulism probably secondary to the inhalation of serotype B toxin from contaminated food. This observation emphasizes that although the clinical diagnosis of botulism is fairly straighforward as it is based on highly indicative symptoms (multiple paralysis of the cranial nerves and atropinic signs), the route of acquisition is not always easy to determine.     

Type E botulism

There are seven known serotypes of botulism, designated A through G; almost all human cases of botulism are caused by types A, B, and E. Botulism type E is the predominant serotype causing disease associated with native Arctic foods. In the circumpolar regions of the world, the coastal soils are rich in botulism type E, and consumption of fish and marine animals in these areas are the sources of clusters of botulism. Unlike spores of type A and B, botulism type E can withstand freezing down to 3.5°C. Alaskan native fermentation of fish heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum toxin to be elaborated from Clostridium botulinum. The consumption of whale meat, "muktuk" has also been associated with outbreaks of botulism in Alaska and the Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been associated with Norwegian "rakfisk" prepared by a process similar to fermented Alaskan foods. Outbreaks in Egypt with the salted gray mullet "faseikh", in Israel and New York linked to salted uneviscerated whitefish "kapchunka", in Iran from eating "ashbal" an uncooked salmon, and in Japan with "izushi" a traditional fermented fish preserved in rice have occurred. Importation of vacuum-packed whitefish from Alaska and Canada has also been associated with sporadic cases of botulism type E in Europe. In March 2010, the Center for Disease Control and Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under an Investigational New Drug program, as the preferred treatment for food-borne botulism, including type E, which had not been covered by the bivalent antitoxin, the prior approved antitoxin product in the USA.     

Clostridium botulinum: an increasing complication of heroin misuse.

Wound botulism is a rare infectious disease due to neurotoxin release from the anaerobic, spore-forming bacterium Clostridium botulinum that is becoming an ever more frequent complication of parenteral drug abuse in the Western world. Before the year 2000, no such cases had been reported in the UK and Ireland, but since then the number of proven and suspected cases of wound botulism occurring in parenteral drug users has increased markedly. The diagnosis is often difficult, based on a high degree of clinical suspicion and if not considered in the initial differential diagnosis, then considerable delays in treatment may result. This is the case report of a male heroin user who presented three times to an Emergency Department in the UK before a diagnosis of wound botulism was made and treatment commenced. It is important that emergency clinicians are aware of the possibility of wound botulism in parenteral drug users that present with unusual neurological or respiratory symptomatology.     

Infantile botulism

We present the first two known cases of infantile botulism in Oklahoma. The first case was due to type B toxin; the second was due to type A toxin. Both cases demonstrate most of the classic features of what now appears to be the most common form of botulism. Infantile botulism is an underrecognized but reversible cause of hypotonia. In most cases, the prognosis is excellent with institution of appropriate supportive care. The recognition of cranial nerve palsies or a history of constipation should raise the suspicion of infantile botulism. Aminoglycoside antibiotics and other agents that may precipitate or exacerbate neuromuscular blockade should be used with extreme caution in hypotonic infants until the cause of the hypotonia is clearly identified.     

Complications and adverse reactions with the use of botulinum toxin

Botulinum toxins are the causative agents of the severe food-borne illness botulism. With lethal doses approximating 10(-9) g/kg body weight, these neurotoxins represent some of the most toxic naturally occurring substances. Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle spasms with adverse effects being typically self-limited. This article deals with some of the complications that have occurred with these treatments. The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent treatment. Prevalence of resistance is less than 5%. Most complications associated with its aesthetic use are few and anecdotal. Nevertheless, the common problems and pitfalls associated with aesthetic treatment of the various areas of the face and neck with botulinum toxin are discussed. Also included are recommendations as to how to avoid these very undesirable, yet common, problems.     

A common antigenic determinant found in two functionally unrelated toxins

The heat-stable enterotoxin ST Ib produced by enterotoxigenic E. coli strains shares a sequence homology with the sea snail neurotoxin, conotoxin GI. Rabbit antisera were raised against synthetic analogs of these toxins and to a six-residue peptide representing the region common to both toxins. Results from enzyme-linked immunosorbent assays indicate that the homologous region of both toxins represents part of their antigenic site. The lack of cross-reactivity exhibited by the six- residue common domain with serum directed against either toxin suggests that this region probably retains a similar conformation in the intact toxins but not in the isolated fragment.     

Mode of action of botulinum neurotoxin: pathological, cellular and molecular aspect]

Several bacteria of the Clostridium genus (C. botulinum) produce 150 kDa di-chainal protein toxins referred as botulinum neurotoxins or BoNTs. They associate with non-toxic companion proteins and form a complex termed botulinum toxin or BoTx. The latter is used in clinic for therapeutic purpose. BoNTs affect cholinergic nerve terminals in periphery where they block acetylcholine release, thereby causing dysautonomia and motorparalysis (i.e. botulism). The cellular action of BoNTs can be depicted according to a three steps model: binding, internalisation and intraneuronal action. The toxins heavy chain mediates binding to specific receptors followed by endocytotic internalisation of BoNT/receptor complex. BoNT receptors may comprise gangliosides and synaptic vesicle-associated proteins as synaptotagmins. Vesicle recycling induces BoNT internalisation. Upon acidification of vesicles, the light chain of the neurotoxin is translocated into the cytosol. Here, this zinc-endopeptidase cleaves one or two among three synaptic proteins (VAMP-synaptobrevin, SNAP25, and syntaxin). As the three protein targets of BoNT play major role in fusion of synaptic vesicles at the release sites, their cleavage is followed by blockage of neurotransmitter exocytosis. The duration of the paralytic effect of the BoNTs is determined by 1) the turnover of their protein target; 2) the time-life of the toxin light chain in the cytosol, and 3) the sprouting of new nerve-endings that are retracted when the poisoned nerve terminal had recovered its full functionality.     

Infantile Botulism: A Case Report and Review

Background

Infantile botulism is the result of ingestion of Clostridium botulinum spores, and is the most common form of infection with botulism in the United States. Ninety percent of cases occur in infants <6 months old. The infants typically present with vague symptoms such as hypotonia and poor feeding. This article reports an infant with confirmed infantile botulism that presented to the Emergency Department (ED) with complaints of decreased feeding and absence of bowel movements for >1 week.

Objectives

Review a case of infantile botulism, its diagnosis, and treatment.

Case Report

A 4-month-old healthy Caucasian male presented to the ED with a 6-day history of decreased feeding after referral from the pediatrician. He had not had a bowel movement for 9 days, and his parents were also concerned about increasing weakness, as he was no longer able to hold his head up on his own. In the ED, he was minimally interactive. His vital signs were within normal limits, and he had hypoactive bowel sounds and decreased tone throughout. He was admitted to the Children's Hospital and eventually transferred to the Pediatric Intensive Care Unit requiring intubation and mechanical ventilation. The botulism immunoglobulin was administered, and a diagnosis was confirmed with positive botulinum toxin in the stool samples. Full recovery was made by the infant.

Conclusion

Awareness of the symptoms of botulism and a high degree of clinical suspicion is needed to make a prompt diagnosis.     

Botulism Outbreak in a Regional Community Hospital: Lessons Learned in Transfer and Transport Considerations

Botulism is a potentially lethal disease caused by a toxin released by Clostridium botulinum. Outbreaks of botulism from food sources can lead to a Mass Casualty Incident (MCI) involving sometimes hundreds of individuals. We report on a recent outbreak of botulism treated at a regional community hospital with a focus on emergency medical services (EMS) response and transport considerations. Case Presentation: There were 53 patient evaluated for botulism at the sending facility. In total, 11 botulism exposures required intubation at the sending facility. Twenty-four patients were ultimately transported by critical care capable ALS crews with the majority (16) of these transports occurred in the first 24?hours. There was one fatality in the first days of the outbreak and a second death that occurred in a patient who died after long-term acute care (LTAC) placement several months after hospital discharge. Conclusion: Local EMS providers and public safety officers have a critical role in identifying and following up on potentially exposed botulism cases. The organization of transporting agencies and the logistics of transfer turned out to be 2 opportunities for improvement in response to this mass casualty incident.     

Botulism Questionnaire: A tactical tool for community use in a mass casualty incident

A botulism-induced mass casualty incident has the potential to severely compromise a community's health-care infrastructure, based upon its lethality, rare occurrence, and duration of symptoms, which require extensive support and care. Although early recognition and treatment with antitoxin or botulism immunoglobulin are essential to the effective management of this type of an incident, the two major challenges in recognition and treatment are the hundreds, if not thousands, of casualties or potential casualties requiring rapid screening and the fact that most clinicians remain ignorant of the management of botulism. The purpose of this article is to present the Botulism Questionnaire, which will assist with the screening of casualties, provide educational and diagnostic cues for clinicians and the lay public, and create a layer of protection for the health-care infrastructure. The applications of this questionnaire in various formats, the numerous points of distribution, and the variety of platforms from which it can be launched will be explored.