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The Cochrane Database of Systematic... Apr 2019Botulism 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Botulinum Toxins; Botulism; Critical Care; Hospitalization; Humans; Immunoglobulins; Immunoglobulins, Intravenous; Infant; Parenteral Nutrition; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 30993666
DOI: 10.1002/14651858.CD008123.pub4 -
Current Developments in Diagnostic Assays for Laboratory Confirmation and Investigation of Botulism.Journal of Clinical Microbiology Apr 2022Detection of botulinum neurotoxin or isolation of the toxin-producing organism is required for the laboratory confirmation of botulism in clinical specimens. In an... (Review)
Review
Detection of botulinum neurotoxin or isolation of the toxin-producing organism is required for the laboratory confirmation of botulism in clinical specimens. In an effort to reduce animal testing required by the gold standard method of botulinum neurotoxin detection, the mouse bioassay, many technologies have been developed to detect and characterize the causative agent of botulism. Recent advancements in these technologies have led to improvements in technical performance of diagnostic assays; however, many emerging assays have not been validated for the detection of all serotypes in complex clinical and environmental matrices. Improvements to culture protocols, endopeptidase-based assays, and a variety of immunological and molecular methods have provided laboratories with a variety of testing options to evaluate and incorporate into their testing algorithms. While significant advances have been made to improve these assays, additional work is necessary to evaluate these methods in various clinical matrices and to establish standardized criteria for data analysis and interpretation.
Topics: Animals; Biological Assay; Botulinum Toxins; Botulism; Clostridium botulinum; Humans; Laboratories; Mice; Serogroup
PubMed: 34586891
DOI: 10.1128/JCM.00139-20 -
Schweizer Archiv Fur Tierheilkunde Oct 2006In Switzerland, the incidence of equine botulism and acute pasture myodystrophy have remarkably increased in the last five years. Equine fodder-borne botulism in Europe... (Review)
Review
In Switzerland, the incidence of equine botulism and acute pasture myodystrophy have remarkably increased in the last five years. Equine fodder-borne botulism in Europe is most likely caused by Clostridium botulinum types C and D that produce the toxins BoNT/C and BoNT/D. Horses showing signs suggestive of botulism (muscle weakness and tremors, reduced tongue tone, slow chewing, salivation and difficulties swallowing, drooping eyelids, mydriasis), especially patients that have fed on suspect fodder (mostly haylage), must be treated with anti-serum as soon as possible. They also need intensive care, which is often difficult to provide and always expensive in the face of a guarded to poor prognosis. Therefore, prevention (high standards of forage quality and vaccination) is all the more important. Pasture myodystrophy is an acute disease with signs of rhabdomyolysis and lethality rate over 90%. It affects grazing horses under frosty, windy and rainy conditions. Preliminary results indicate that Clostridium sordellii and Clostridium bifermentans producing lethal toxin may play a role in pasture myodystrophy. Our efforts concentrate on developing a new subunit vaccine for equine botulism and understanding the ethiology and pathogenesis of pasture myodystrophy with the goal of improving prevention against these highly fatal diseases that present a significant risk to our horse population.
Topics: Animal Feed; Animals; Bacterial Vaccines; Botulinum Toxins; Botulism; Clostridium botulinum; Communicable Diseases, Emerging; Horse Diseases; Horses; Muscular Dystrophy, Animal; Soil Microbiology; Switzerland
PubMed: 17076463
DOI: 10.1024/0036-7281.148.10.553 -
American Family Physician Apr 2002Although the worldwide incidence of infant botulism is rare, the majority of cases are diagnosed in the United States. An infant can acquire botulism by ingesting... (Review)
Review
Although the worldwide incidence of infant botulism is rare, the majority of cases are diagnosed in the United States. An infant can acquire botulism by ingesting Clostridium botulinum spores, which are found in soil or honey products. The spores germinate into bacteria that colonize the bowel and synthesize toxin. As the toxin is absorbed, it irreversibly binds to acetylcholine receptors on motor nerve terminals at neuromuscular junctions. The infant with botulism becomes progressively weak, hypotonic and hyporeflexic, showing bulbar and spinal nerve abnormalities. Presenting symptoms include constipation, lethargy, a weak cry, poor feeding and dehydration. A high index of suspicion is important for the diagnosis and prompt treatment of infant botulism, because this disease can quickly progress to respiratory failure. Diagnosis is confirmed by isolating the organism or toxin in the stool and finding a classic electromyogram pattern. Treatment consists of nutritional and respiratory support until new motor endplates are regenerated, which results in spontaneous recovery. Neurologic sequelae are seldom seen. Some children require outpatient tube feeding and may have persistent hypotonia.
Topics: Botulinum Antitoxin; Botulism; Clostridium botulinum; Diagnosis, Differential; Electromyography; Humans; Infant; Infant, Newborn; United States
PubMed: 11996423
DOI: No ID Found -
Vaccine Feb 2018Botulinum neurotoxins (BoNT) are the most toxic proteins for humans. BoNTs are single chain proteins with an N-terminal light chain (LC) and a C-terminal heavy chain...
Botulinum neurotoxins (BoNT) are the most toxic proteins for humans. BoNTs are single chain proteins with an N-terminal light chain (LC) and a C-terminal heavy chain (HC). HC comprises a translocation domain (HC) and a receptor binding domain (HC). Currently, there are no approved vaccines against botulism. This study tests a recombinant, full-length BoNT/A1 versus LCHC/A1 and HC/A1 as vaccine candidates against botulism. Recombinant, full-length BoNT/A1 was detoxified by engineering 3-amino acid mutations (E224A/R363A/Y366F) (M-BoNT/A1) into the LC to eliminate catalytic activity, which reduced toxicity in a mouse model of botulism by >10-fold relative to native BoNT/A1. As a second step to improve vaccine safety, an additional mutation (W1266A) was engineered in the ganglioside binding pocket, resulting in reduced receptor binding, to produce M-BoNT/A1. M-BoNT/A1 vaccination protected against challenge by 10 LD Units of native BoNT/A1, while M-BoNT/A1 or M-BoNT/A1 vaccination equally protected against challenge by native BoNT/A2, a BoNT subtype. Mice vaccinated with M-BoNT/A1 surviving BoNT challenge had dominant antibody responses to the LCHC domain, but varied antibody responses to HC. Sera from mice vaccinated with M-BoNT/A1 also neutralized BoNT/A1 action on cultured neuronal cells. The cell- and mouse-based assays measured different BoNT-neutralizing antibodies, where M-BoNT/A1 elicited a strong neutralizing response in both assays. Overall, M-BoNT/A1, with defects in multiple toxin functions, elicits a potent immune response to BoNT/A challenge as a vaccine strategy against botulism and other toxin-mediated diseases.
Topics: Animals; Antibodies, Bacterial; Antibodies, Neutralizing; Antigens, Bacterial; Bacterial Vaccines; Botulinum Toxins; Botulism; Clostridium botulinum; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Epitopes; Humans; Immunization; Mice; Neurons; Recombinant Proteins
PubMed: 29307477
DOI: 10.1016/j.vaccine.2017.12.064 -
Journal of Infection in Developing... Mar 2024Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A)... (Review)
Review
INTRODUCTION
Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application.
CASE PRESENTATIONS
In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application.
RESULTS
The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended.
CONCLUSIONS
Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.
Topics: Humans; Botulinum Toxins; Botulism; Botulinum Antitoxin; Paralysis; Iatrogenic Disease; Clostridium botulinum; Botulinum Toxins, Type A
PubMed: 38635607
DOI: 10.3855/jidc.18868 -
Foodborne Pathogens and Disease Apr 2021We aim to identify possible biological, social, and economic factors that could influence the prevalence of foodborne botulism (FB). The objective of this article is to...
We aim to identify possible biological, social, and economic factors that could influence the prevalence of foodborne botulism (FB). The objective of this article is to assess epidemiological peculiarities of FB in Ukraine from 1955 to 2018 using national epidemiological surveillance data. This article presents an epidemiological descriptive population-based study of the epidemiology of FB using correlation analysis. From 1955 to 2018, 8614 cases of botulism were recorded in Ukraine causing 659 deaths. The distribution of types of botulism toxins is represented by type A (7.97%), B (59.64%), suspected as C (0.56%), E (25.47%), others (5.33%), and unidentified (1.04%). From 1990 to 2015, the rate correlation between Human Development Index (HDI) and incidence of botulism was -0.75 ± 0.20. Homemade canned meat and fish continue to be the leading causes of botulism in Ukraine. Cases related to commercial food were rare or absent, but in recent years (2017-2018), their percentage has increased to 32.56%. The HDI and botulism have an inverse mathematical correlation and predictable logical relationship: with an HDI increase, the incidence of FB decreased. In general, food botulism in Ukraine is related to traditional socioeconomic factors related to cultural food habits. In the face of declining living standards and uncertainty that food products will be physically or economically available, homemade preservation increases. Home food preservation is a major cause of botulism in Ukraine. The elimination of FB is possible in Ukraine only with the complete cessation of home canning and state control over the manufacture and sale of commercial canned products.
Topics: Agaricales; Botulism; Clostridium botulinum; Feeding Behavior; Food Microbiology; Food Preservation; Humans; Incidence; Meat Products; Population Surveillance; Prevalence; Risk Factors; Seafood; Socioeconomic Factors; Ukraine; Vegetables
PubMed: 33332209
DOI: 10.1089/fpd.2020.2826 -
BMJ (Clinical Research Ed.) Aug 1992
Topics: Botulism; Food Preservation; Humans; Risk Factors
PubMed: 1392853
DOI: 10.1136/bmj.305.6848.264 -
Toxins Sep 2020Group I and are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of Group I...
Group I and are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of Group I and (including 417 newly sequenced strains) has been carried out to characterise the genetic diversity and spread of these bacteria and their neurotoxin genes. Core genome single-nucleotide polymorphism (SNP) analysis revealed two major lineages; Group I (most strains possessed botulinum neurotoxin gene(s) of types A, B and/or F) and (some strains possessed a type B botulinum neurotoxin gene). Both lineages contained strains responsible for foodborne, infant and wound botulism. A new cluster was identified that included five strains with a gene encoding botulinum neurotoxin sub-type B1. There was significant evidence of horizontal transfer of botulinum neurotoxin genes between distantly related bacteria. Population structure/diversity have been characterised, and novel associations discovered between whole genome lineage, botulinum neurotoxin sub-type variant, epidemiological links to foodborne, infant and wound botulism, and geographic origin. The impact of genomic and physiological variability on the botulism risk has been assessed. The genome sequences are a valuable resource for future research (e.g., pathogen biology, evolution of and its neurotoxin genes, improved pathogen detection and discrimination), and support enhanced risk assessments and the prevention of botulism.
Topics: Botulinum Toxins; Botulism; Clostridium; Clostridium botulinum; Genome, Bacterial; Genotype; Humans; Infant; Molecular Epidemiology; Phenotype; Phylogeny; Polymorphism, Single Nucleotide; Whole Genome Sequencing; Wound Infection
PubMed: 32932818
DOI: 10.3390/toxins12090586 -
ACS Infectious Diseases Aug 2022Botulinum neurotoxin serotype A (BoNT/A) is recognized by the Centers for Disease Control and Prevention (CDC) as the most potent toxin and as a Tier 1 biowarfare agent....
Botulinum neurotoxin serotype A (BoNT/A) is recognized by the Centers for Disease Control and Prevention (CDC) as the most potent toxin and as a Tier 1 biowarfare agent. The severity and longevity of botulism stemming from BoNT/A is of significant therapeutic concern, and early administration of antitoxin-antibody therapy is the only approved pharmaceutical treatment for botulism. Small molecule therapeutic strategies have targeted both the heavy chain (HC) and the light chain (LC) catalytic active site and α-/β-exosites. The LC translocation mechanism has also been studied, but an effective, nontoxic inhibitor remains underexplored. In this work, we screened a library of salicylanilides as potential translocation inhibitors. Potential leads following a primary screen were further scrutinized to identify sal, which has a cellular minimal concentration of a drug that is required for 50% inhibition (IC) value of 141 nM. The inquiry of salicylanilide sal's mechanism of action was explored through a self-quenched fluorogenic substrate conjugated to bovine serum albumin (DQ-BSA) fluorescence, confocal microscopy, and vacuolar H-ATPase (V-ATPase) inhibition assays. The summation of these findings imply that endolysosomal proton translocation through the protonophore mechanism of sal causes endosome pH to increase, which in turn prevents LC translocation into cytosol, a process that requires an acidic pH. Thus, the inhibition of BoNT/A activity by salicylanilides likely occurs through disruption of pH-dependent endosomal LC translocation. We further probed BoNT inhibition by sal using additivity analysis studies with bafilomycin A1, a known BoNT/A LC translocation inhibitor, which indicated the absence of synergy between the two ionophores.
Topics: Botulism; Catalytic Domain; Humans; Salicylanilides; Serogroup; United States
PubMed: 35877209
DOI: 10.1021/acsinfecdis.2c00230