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BACKGROUND: Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011. OBJECTIVES: To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi‐RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food‐borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human‐derived botulinum immune globulin intravenous (BIG‐IV), plasma exchange, 3,4‐diaminopyridine, and guanidine. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. Our primary outcome was in‐hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment. MAIN RESULTS: A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG‐IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention‐to‐treat principles, and possibly some between‐treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG‐IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) ‐3.10 weeks, 95% CI ‐4.52 to ‐1.68; moderate‐certainty evidence); mechanical ventilation (BIG‐IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD ‐2.60 weeks, 95% CI ‐4.06 to ‐1.14; low‐certainty evidence); and tube or parenteral feeding (BIG‐IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD ‐6.40 weeks, 95% CI ‐10.00 to ‐2.80; moderate‐certainty evidence), but not on proportion of participants with adverse events or complications (BIG‐IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to ‐0.11; moderate‐certainty evidence). AUTHORS' CONCLUSIONS: We found low‐ and moderate‐certainty evidence supporting the use of BIG‐IV in infant intestinal botulism. A single RCT demonstrated that BIG‐IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

The aim of this study was to determine the prevalence of Clostridium botulinum in honey samples using conventional methods and multiplex PCR (mPCR). A total number of 150 honey samples were randomly collected from apiaries, retail shops, weekly open bazaars, and supermarkets in Samsun, Turkey. Of 150 honey samples, 4 (2.6%) were positive for the botulinum neurotoxin gene by mPCR analysis. A total of 4 C. botulinum isolates were obtained from the mPCR positive samples, of which 3 were type A and 1 was type B. No samples were positive regarding the type E and type F neurotoxin genes. This is the first report of type A and type B spores of C. botulinum being detected and isolated in Turkey. This study revealed that some honey samples may present a potential hazard for food borne and infant botulism.

Proteolytic Clostridium botulinum type B strains were investigated for stability of toxigenicity and bont/b gene upon serial passage. Strains with bont/b gene located on their plasmids showed loss or decrease of toxigenicity during serial passage. Some strains lost the bont/b gene-encoding plasmid. The stability of the plasmids varied between strains.

Seven serologically related, but antigenically different, botulinum toxins (BoNTs) have been identified including types A, B, C, D, E, F, and G. The bacterium Clostridium botulinum along with some strains of Clostridium baratti and Clostridium butyricum are known to produce botulinum toxins responsible for 4 forms of botulism poisoning including food-borne botulism, inhalation botulism, wound botulism, and infant botulism. Botulism toxins consist of a heavy chain (100 kDa), responsible for binding to target cells, and a light chain (50 kDa) responsible for catalytic protein cleaving activity. Light chain has been identified as a zinc endopeptidase that cleaves proteins forming the synaptic vesicle docking and fusion complex (Simpson 1996; Lacy and Stevens 1997). The standard for detection of BoNT toxins is the mouse bioassay, which is able to detect as little as 0.02 ng of toxin. Strengths of the mouse bioassay include conceptual simplicity and sensitivity. While the non-selectivity of the mouse bioassay enables it to detect any BoNT serotype, additional neutralization assays are necessary to determine serotype. Other limitations of the mouse bioassay include expense, expertise related to maintaining mouse-rearing facilities, and time, because as much as 4 d may be required to obtain results (Hallis and others 1996; Witcome and others 1999). Several attempts to replace the mouse bioassay have been made. Methods that have been developed and hold promise for future replacement of the mouse bioassay include mass spectroscopy, immunoassays, polymerase chain reaction (PCR) assays, and assays based upon protease activities of BoNTs. Currently, no single assay appears to be capable of replacing the broadly applicable mouse bioassay.

Within a 3-month period, two infants presented non-specifically to hospital and rapidly progressed developing flaccid paralysis. Both children were diagnosed with infant botulism. We briefly review these two cases and discuss the diagnostic and management issues involved with this rare childhood disease.

"Shaker foal" disease, toxicoinfectious botulism of foals, was 1st described as a clinical entity in 1967. The reported mortality rate was 90%, with death occurring within 24-72 hours of the onset of the characteristic clinical signs. The mortality rate decreased when equine-origin botulism antitoxin became available; however, a certain percentage of foals continued to die of respiratory failure. Mechanical ventilation is an important part of the treatment of infant botulism and is essential to the survival of many affected infants. We report a retrospective study of 9 foals with toxicoinfectious botulism where early mechanical ventilation was employed as part of the treatment. Foals receiving mechanical ventilation were progressively acidemic and had increased PaCO2 tensions before mechanical ventilation. These arterial blood gas abnormalities were ameliorated with mechanical ventilation. One foal was euthanized for economic reasons; survival in treated foals was 87.5%. Mechanical ventilation of foals with botulism and respiratory failure appears to be an effective therapy.

Infant botulism, a disease that results in a blockade of voluntary motor and autonomic functions, was first recognized in the United States in the late 1970s. Since then, more than 1000 cases in this country have been reported to the Centers for Disease Control and Prevention (CDC). Numerous studies have shown that the ingestion of honey is linked with infant botulism. In addition, honey samples across the United States have tested positive for Clostridium botulinum spores and toxins. Such substantial evidence led the CDC to recommend that honey not be given to infants younger than 12 months old. It is important that clinicians be familiar with this risk and should not recommend honey-containing products or supplements or the use of honey as a flavoring agent for infants in this age group.

Objective: The study goal was to understand the incidence, etiology, and management of airway complications in infant botulism. Methods: We conducted a retrospective review of the period from January 1, 1987, to December 31, 1997. Setting: Urban tertiary care children's hospital. Results: Of 60 children with infant botulism, 37 (61.7%) required endotracheal intubation for a mean of 21 days. No patient required a tracheostomy. Airway complications (stridor, subglottic stenosis, granuloma formation) occurred in 5 (13.5%) of 37 patients, with 3 requiring surgical bronchoscopy. Of the 37 children, 14 (37.8%), including 4 with airway complications, had endotracheal tube leak pressures recorded. In 3 (50%) of 6 patients with measured leak pressures of greater than 40 cm H2O, airway complications developed. Complications did not develop in patients with leak pressures of less than 20 cm H2O. No correlation between length of intubation and complications could be established. Conclusion: Airway complications in infant botulism may be accompanied by high leak pressures and can be managed with endoscopic techniques. The study data suggest that leak pressures should be measured on a regular basis and maintained at less than 20 to 25 cm H2O. A prospective trial to study this issue is warranted. Tracheotomy is not routinely necessary. A high index of suspicion, early diagnosis, and prompt intervention are required for the optimal management of airway complications in infant botulism. (Otolaryngol Head Neck Surg 2002;126:234-9.)

The principal electrodiagnostic feature of infant botulism, an incremental response on high rates of repetitive nerve stimulation, has variable sensitivity and may not always be useful as a diagnostic test given the vagaries of test timing and severity of illness. We report the use of stimulation single fiber EMG (S-SFEMG) in making this clinical diagnosis. Four infants between 1 and 5 months of age presented with rapidly progressive bulbar and limb weakness, internal and external ophthalmoplegia, areflexia, and compromised ventilation. Incremental response with high-rate repetitive nerve stimulation and a typical clinical course for infant botulism confirmed the diagnosis in all; stool toxin studies were positive for type B botulinum in 2 of the 3 cases in which they were obtained. S-SFEMG was performed by surface stimulation of median and ulnar nerves and recording with a single fiber needle in the thenar, hypothenar, or first dorsal interosseous muscles. A total of eight single fiber recordings were studied at rates of 2, 5, 10, and 20 Hz. All single fibers studies showed an improvement with higher rates of stimulation, beginning at 10 Hz and peaking at 20 Hz. Compared to baseline study at 2 Hz (100%), the mean percent changes in jitter at 5, 10, and 20 Hz were 109, 60, and 47, respectively. This is the first report of the usefulness of S-SFEMG in the diagnosis of infant botulism.

Botulism is a paralyzing disease caused by the toxin of Clostridium botulinum. The toxin produces skeletal muscle paralysis by producing a presynaptic blockade to the release of acetylcholine. Recent studies have pinpointed the site of action of the several types of botulinum neurotoxin at the nerve terminal. Since the discovery of the toxin about 100 years ago, five clinical forms of botulism have been described: 1) classic or foodborne botulism; 2) wound botulism; 3) infant botulism; 4) hidden botulism; 5) inadvertent botulism. A clinical pattern of descending weakness is characteristic of all five forms. Almost all human cases of botulism are caused by one of three serotypes (A, B, or E). Classic and wound botulism were the only two forms known until the last quarter of this century. Wound botulism was rare until the past decade. Now there are increasing numbers of cases of wound botulism in injecting drug users. Infant botulism, first described in 1976, is now the most frequently reported form. In infant botulism spores of Clostridium botulinum are ingested and germinate in the intestinal tract. Hidden botulism, the adult variant of infant botulism, occurs in adult patients who usually have an abnormality of the intestinal tract that allows colonization by Clostridium botulinum. Inadvertent botulism is the most recent form to be described. It occurs in patients who have been treated with injections of botulinum toxin for dystonic and other movement disorders. Laboratory proof of botulism is established with the detection of toxin in the patient's serum, stool, or wound. The detection of Clostridium botulinum bacteria in the stool or wound should also be considered evidence of clinical botulism. Electrophysiologic studies can provide presumptive of botulism in patients with the clinical signs of botulism. Electrophysiologic testing can be especially helpful when bioassay studies are negative. The most consistent electrophysiologic abnormality is a small evoked muscle action potential in response to a single supramaximal nerve stimulus in a clinically affected muscle. Posttetanic facilitation can be found in some affected muscles. Single-fiber EMG studies typically reveal increased jitter and blocking, which become less marked following activation. The major treatment for severe botulism is advance medical and nursing supportive care with special attention to respiratory status.

KEVENK, Tahsin Onur/0000-0003-2519-8060; WOS: 000333886000023 PubMed: 24621137 The aim of this study was to determine the prevalence of Clostridium botulinum in honey samples using conventional methods and multiplex PCR (mPCR). A total number of 150 honey samples were randomly collected from apiaries, retail shops, weekly open bazaars, and supermarkets in Samsun, Turkey. Of 150 honey samples, 4 (2.6%) were positive for the botulinum neurotoxin gene by mPCR analysis. A total of 4 C. botulinum isolates were obtained from the mPCR positive samples, of which 3 were type A and 1 was type B. No samples were positive regarding the type E and type F neurotoxin genes. This is the first report of type A and type B spores of C. botulinum being detected and isolated in Turkey. This study revealed that some honey samples may present a potential hazard for food borne and infant botulism. Univ. of Ondokuz Mayis, Scientific Research CenterOndokuz Mayis University [PYO.VET.1901.11.012] This study was supported by the Univ. of Ondokuz Mayis, Scientific Research Center, under the project nr.: PYO.VET.1901.11.012. The authors thank Univ. of Helsinki, Faculty of Veterinary Medicine, Dept. of Food Hygiene and Environmental Health for the positive DNA samples.

The neurotoxin associated with type A infant botulism in Japan shows different antigenic properties from those produced by authentic strains. The monoclonal antibodies recognizing the light chain reacted to both neurotoxins, whereas half the antibodies recognizing the heavy chain reacted specifically to the respective neurotoxin. Each neurotoxin showed its own manner of binding to brain synaptosomes. These results indicate that the distinguishable characteristics are ascribable to the heavy chain but not to the light chain. In both neurotoxins, an epitope recognized by the monoclonal antibody that reacts to the light chain and neutralizes the toxin was found to be very close to the amino-terminal half (H-1 fragment) of the heavy chain. This may support the hypothesis that the H-1 fragment functions in the transport of the light chain in the target cell.

The germination of spores of a neurotoxigenic Clostridium butyricum strain (BL 6340), which was isolated from infant botulism in Italy, and that of a nontoxigenic C. butyricum type strain (NCIB 7423) were studied. The spores of BL 6340 strain were killed at 80 C for 10 min, and required the mixture of L-alanine, L-lactate, glucose and bicarbonate for their optimal germination. These characteristics are the same as those of Clostridium botulinum type E strain, but different from those of NCIB 7423 strain. In a hybridization test, however, the labeled DNAs extracted from NCIB 7423 strain highly (98%) hybridized to the DNAs of the BL 6340 strain, but little (45%) to the DNAs of C. botulinum type E strain. The biochemical properties of the BL 6340 and NCIB 7423 strains were identical, but different from those of C. botulinum type E. These data confirmed that the BL 6340 strain belongs to C. butyricum species, but that only its characteristics of toxin production, its minimum requirements for germination, and the behavior of its spores to heat treatment are the same as those of C. botulinum type E. When conventionally raised suckling mice were injected with 5 x 10(7) spores of BL 6340 strain intra- or orogastrically, botulism was not observed. However, 8- to 13-day-old mice had type E botulinum toxin in the large intestine 3 days after introduction of its spores.

A nested polymerase chain reaction was utilized to successfully detect the type B botulinum neurotoxin gene of Clostridium botulinum in feces from a 6-month-old patient, who had already been diagnosed with type B infant botulism by mouse bio-assay. This method of rapid diagnosis without enrichment culture of feces can be applied to other types of toxins in the use of the type-specific primers. Further investigations, however, are required to define the sensitivity and specificity of the method.

Clostridium butyricum long known to cause spoilage in canned acid foods recently caused two separate cases of infant botulism in Italy by strains producing type E botulinum toxin. Heat resistance of spores of toxigenic and nontoxigenic C. butyricum was determined. The non-toxigenic strain was considerably more heat resistant, having a D-value at 212°F of 4.7 min compared to a D-value 170°F of 2.3–2.5 min for toxigenic strains at pH 7.0. Minimum pH for growth and toxin production was also determined. The nontoxigenic strain grew at pH 4.2; toxigenic strains grew and produced toxin at pH 5.2 but not at pH 5.0.

We report on 3 infants who had relapse of infant botulism after apparent resolution of clinical symptoms. This group represented 5% of the infants with confirmed infant botulism who were treated at our institution since 1976. The exact cause for these relapses was unclear, but three potential mechanisms are examined. There were no historical, clinical, or electrophysiological predictors of relapse. Although at the time of writing recovery from relapse appeared complete, close follow-up of patients recovering from a bout of infant botulism is necessary.

Clostridium botulinum is an anaerobic, Gram-positive, spore-forming rod that produces a potent neurotoxin. Seven types (A, B, C1+2, D, E, F and G) of C botulinum are recognised, based on the antigenic specificity of the botulinum neurotoxin (BoNT) produced by each strain. Types A, B, E and F cause human botulism, while types B, C and D cause disease in farm animals (Goonetilleke and Harris 2004, Simpson 2004, Radostits and others 2007, Popoff and Bouvet 2009). Animals most commonly affected are wild fowl and poultry, cattle, horses and some species of fish. There are three major recognised disease entities in humans, food-borne botulism, infant botulism and wound botulism . Recently, Rodloff and Kruger (2012) suggested that a new form of chronic, visceral botulism may exist that affects both human beings and animals. The antagonism between C botulinum and bacterial members of the microecosystem …

The isolation of Clostridium botulinum from the home environment of New South Wales patients with infant botulism is reported. Of the three cases of infant botulism type B, the bacteria were isolated from soil around the dwelling in one, and from tank rainwater in another. In one case with type A, the bacteria were present in the soil, vacuum-cleaner dust, and tank rainwater. The bacteria were not detected in the environment of two adult patients and a child with C. botulinum in their stools. The home location of the patients with infant botulism, and the frequency of isolation of the bacteria from rainwater, soil and vacuum-cleaner dust in Cobar, Nyngan, some Sydney suburbs, and at five pastoral homesteads suggest that infants in rural areas are more at risk than those in large metropolitan areas. The age of the infants with diagnosed botulism in New South Wales, compared with those reported in the United States data, strongly suggests that the disease is not being fully recognised in younger infants.

Infantile botulism is a recently recognized cause of acute hypotonic paresis and respiratory failure in young infants. Electrophysiological testing has proven useful in early diagnosis in suspected cases by demonstrating abnormal neuromuscular transmission as is known to occur in botulism. Twenty-five infants with bacteriologically proven botulism were studied by uniform methods in our laboratory and characteristic electrophysiological abnormalities were found. Repetitive stimulation at 20 and 50 Hz was the most specific single test; 23 patients (92%) showed incremental responses. Stimulation at low rates was less specific. Concentric needle electromyography provided useful supplemental information. Short-duration, low-amplitude motor unit potentials were prominent in 22 patients (92%) accompanied by abnormal spontaneous activity in 13 patients (54%). Compound muscle action potential amplitudes were usually reduced, but motor and sensory conduction studies were otherwise normal. Electrodiagnostic testing demonstrated one or more characteristic abnormalities in all cases of infantile botulism. This constellation of electrophysiological abnormalities, combined with an appropriate clinical picture, was so distinctive as to allow early presumptive diagnosis of infant botulism, before the results of bacteriological testing were available.

The syndrome of infant botulism was first recognised in late 1975 and the majority of cases reported have been from the United States of America. One case has been reported from the United Kingdom and one from Canada. A three-month-old male infant from Victoria, Australia presented with constipation, marked hypotonia, limb weakness, ptosis, facial weakness and inability to suck and swallow. These abnormalities resolved and he returned to normal over the ensuing months. A diagnosis of infant botulism was confirmed after the isolation of Clostridium botulinum type B from the faeces. Infant botulism has now been recognised in four different countries and it is likely than with increasing awareness of this striking clinical syndrome, more cases will be identified.

Infant botulism is a rare disease with previous reports in Australia originating from its southern states. The first case to be recognized from Queensland is described in a four-month-old white girl. Complications included respiratory failure, the syndrome of inappropriate antidiuretic hormone secretion, urinary tract infection and autonomic dysfunction.