Iatrogenic Botulism Research Articles

Iatrogenic botulism after intragastric botulinum neurotoxin injections – a major outbreak

BackgroundIntragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI.MethodsWe retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany.ResultsSeven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits.ConclusionOur study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

Iatrogenic botulism after botulinum toxin type A: Five cases

Botulinum toxin A (BTX-A) is frequently used for spasticity, focal dystonia, hemifacial spasm, hyperhidrosis, strabismus, chronic migraine and cosmetic purposes. Therapeutic use is generally safe. It is important to consider the risk of iatrogenic botulism, especially in high dose approved or with unapproved formulations and indications. Five patients with iatrogenic botulism were described. All patient developed systemic symtomps of Botulism following botulinum toxin injection for various reason. Clinical presentatiton, treatment and outcome were explained in this report. Conclusion: Based on the case series reported, we would like to emphasize the important of adhering to recommended dose of approved formulations approved or unapproved indication of BTX-A.

TWO CASE OF BOTULISM DEVELOPED AFTER ENDOSCOPIC CLOSTRIDIUM BOTULINUM TOXIN ADMINISTRATION TO THE STOMACH WALL

Every year, the United States records about 200 cases of botulism. Those who inject substances such as heroin, use homemade alcohol, and eat improperly prepared canned food are at risk of contracting this extremely rare disease. As seen in this case, those treated with Clostridium Botulinum Toxin are also considered to be in the risk group. However, iatrogenic botulism cases are much rare; and in the literature, case reports of botulism after intragastric Clostridium Botulinum Toxin administration are rare. We aimed to present these cases to draw attention to this rare condition in patients who presented to the emergency department with complaints such as weakness, dyspnea, and diarrhea.

The enemy at the gate: Botulism.

Botulism, caused by Clostridium botulinum, continues to pose a significant threat to public health. This review explores the historical context and contemporary relevance of botulism, emphasizing its potential lethality and evolving medical applications. In recent years, the use of botulinum toxin in medical procedures, particularly in cosmetic and therapeutic applications, has increased the risk of iatrogenic botulism. The rise in iatrogenic cases underscores the importance of vigilance among health-care providers, especially those in emergency departments, where prompt diagnosis and intervention are critical. This review underscores the necessity for health-care professionals to consider botulism in the differential diagnosis of patients presenting with relevant symptoms, given the potential severity of the condition.

Efficacy and Safety Analysis of Botox Application and Iatrogenic Botulism: Panacea or Peril?

Clostridium botulinum toxin-A (BoNT-A) creates temporary paralysis in the muscles by acting on the muscle-nerve junction. It is injected into the mimic muscles when a decrease in the movements of the mimic muscles is desired. Despite many favorable applications, the use of BoNT-A is not without drawbacks. Although there is no expected serious side effect on health in BoNT-A treatments, various problems can be encountered in patients treated for aesthetic purposes. Botulism is a rare but potentially life-threatening syndrome, which is caused by the toxin produced by the bacterium Clostridium botulinum, which acts on the nervous system, vegetative forms of C. botulinum can only survive in anaerobic conditions, while spore forms are common in nature and can withstand harsh conditions. Botulism can stem from bacterial spores which release toxin in the body; in the form of enteric botulism, and wound botulism. The cases that develop 'iatrogenic botulism' after such procedures are usually those receiving high-dose toxin for therapeutic purposes. The treatment of botulism mainly consists of anti-toxin therapy and, if necessary, intensive care to prevent organ failures, including respiratory support. This article aims to cover all these issues related to botulism and other adverse outcomes related to BoNT-A injection in light of the most recent literature.

Iatrogenic botulism.

This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.

"Cosmetic" iatrogenic botulism : description of 2 cases in Switzerland

Botulism is a neuro-paralytic syndrome caused by the production of a neurotoxic protein by Clostridium botulinum. It is a rare but potentially fatal poisoning. Symptoms are due to blockage of neurotransmitter release at the neuromuscular junction. Botulism usually occurs following ingestion, inhalation or contact of the toxin with a wound. More recently, cases of iatrogenic botulism have been described, notably following the injection of toxin for therapeutic or cosmetic purposes. In spring 2023, an outbreak of iatrogenic botulism following intragastric injections was reported in Europe. Here, we provide an overview of botulism, followed by a presentation of the only two Swiss cases reported during the epidemic.

A Double-Edged Sword "BoNT" in Hospital Settings From European Region: Iatrogenic Botulism Warranting Enhanced Vigilance.

A Double-Edged Sword "BoNT" in Hospital Settings From European Region: Iatrogenic Botulism Warranting Enhanced Vigilance.

A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023.

In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.

The recent outbreak of Iatrogenic botulism: point of view from the present world: editorial.

The recent outbreak of Iatrogenic botulism: point of view from the present world: editorial.

Botulinum neurotoxin is both poison and medicine: botulinum therapy and iatrogenic botulism

Botulinum neurotoxin is the most potent poison known worldwide. Over the past two centuries, its structure and functions have been studied in detail, and obtained in its pure form. Knowledge of the mechanisms of action of botulinum neurotoxin has determined two directions of its possible use: negative, as a biological (toxin) weapon, and positive, as an agent that eliminates pathological muscle hypertonicity and neuropathic pain and can be used for aesthetic purposes (beauty injections).
 The lecture presents the chronological development of both directions and provides a detailed analysis of the various uses of botulinum neurotoxin as a medical and cosmetic treatment. Particular attention is paid to the side effects of botulinum therapy and ways to overcome them.

A case of asymmetric cranial nerve palsy due to iatrogenic botulism

A case of asymmetric cranial nerve palsy due to iatrogenic botulism

Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021.

SummaryBotulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.

A review on iatrogenic botulism

Background:With the flourishing application of botulinum toxin cosmetically and therapeutically is the emergence of iatrogenic botulism, a new type of botulism in addition to the traditional ones.Objectives:We aim at a comprehensive review of the clinical characteristics of iatrogenic botulism. Methods: The available publications are retrieved and studied.Results:Botulinum toxin blocks cholinergic transmission in the neuromuscular junctions and autonomic ganglia. The blockade can spread from the site of tissue injection to adjacent or sometimes far off structures, resulting in inadvertent disabling or even lethal effects. On literature review, weakness and dysphagia are the commonest complications of iatrogenic botulism, whereas ophthalmological and oropharyngeal symptoms are more prevalent in the cosmetic group and dyspnea in the therapeutic group. Antitoxin therapy is required in about 20% of the patients. Diagnosis of iatrogenic botulism is primarily clinical and should not be confused with the neurological diagnoses possessing similar clinical manifestations. Vigilance to the drug formulation, dosage, and administration during botulinum toxin injection are part of the preventive measures in minimizing the occurrence of iatrogenic botulism.Conclusion:While overlapping with the traditional types of botulism, iatrogenic botulism carries its unique clinical characteristics.

Iatrogenic botulism – a possible cause of generalised muscular weakness in child

Iatrogenic botulism – a possible cause of generalised muscular weakness in child

Investigation of the Frequency of Foodborne Botulism in Patients Referred to Loghman Hospital in Tehran City, Iran, From 2008 to 2019

Background: Foodborne botulism is a fatal paralytic illness caused mainly by the neurotoxin produced by an anaerobic bacterium called Clostridium botulinum. In this study, the frequency of foodborne botulism in patients referred to a hospital in Iran has been reviewed for ten years.Methods: In this routine database study, medical records of patients with foodborne botulism referred to Loghman Hospital in Tehran City, Iran, from March 20, 2008, to March 20, 2019, were reviewed. Information on variables of age, sex, place of residence, food consumed, clinical symptoms of patients (such as dysphagia, nausea, vomiting, ataxia, etc.), toxin type, and length of hospitalization were collected with a researcher-made questionnaire. Finally, the collected data were analyzed in SPSS-24 with descriptive and analytical statistical tests.Results: In this study, 61 suspected botulism patients were clinically diagnosed in Loghman Hospital, of whom 55 patients were clinically suspected of foodborne botulism, 5 patients had iatrogenic botulism, and 1 patient had infant botulism. Of these 55 patients with the clinical diagnosis of foodborne botulism, 19 patients were confirmed by laboratory examinations, and 2 patients died. Sixteen patients confirmed by laboratory had neurotoxin botulinum type A. The mean age of the patients was 36.9 years with a standard deviation of 18.6 years. About 54.5% of the patients were male and 45.5% female. Weaknesses (58.2%), ptosis (droopy eyelid) (56.4%), and diplopia (double vision) (52.7%) were the common clinical symptoms of the patients under study. Canned foods and dairy products were the main foods consumed by the patients. The duration of admission time ranged between 1 and 41 days, with an average of 7.7 days. About 23.64% of patients were admitted to the intensive care unit.Conclusion: The prevalence of foodborne botulism is rare compared with other food poisonings but is still a major public health problem due to the consumption of traditional food products and unboiled canned foods in Iran.

Novel Antidotal Treatment of Botulism Using an FDA‐Approved Small Molecule

Botulinum neurotoxins (BoNTs) are exceedingly potent neuroparalytic toxins which block release of neurotransmitter from motor nerve terminals, causing respiratory failure at lethal doses. The only treatment for botulism is post‐exposure prophylaxis with antitoxin. However, antitoxin is most effective when given prior to symptomatic emergence, and consequently 70% of symptomatic patients require artificial ventilation for a median of two weeks. The voltage‐gated potassium channel antagonist 3,4‐diaminopyridine (DAP) has been proposed as a symptomatic treatment to mitigate muscle weakness in botulism patients. However, experimental support for this hypothesis is lacking.To test the efficacy of DAP in treating toxic signs of botulism, we first evaluated concentration‐dependent effects of DAP on synaptic transmission and muscle function in mouse hemidiaphragm preparations following intoxication by BoNT serotypes A, B or E. For all serotypes, DAP increased quantal content and restored muscle contraction, with effect sizes that were inversely proportional to the degree of paralysis. Based on these findings, we evaluated the effects of human‐equivalent doses of DAP in mice intoxicated with the same BoNT serotypes. In a sublethal intoxication model, DAP transiently increased respiratory function at multiple time points for all serotypes. In lethal challenges with BoNT/A, repeated administration of DAP sustained respiratory function and prolonged survival throughout the treatment period. These findings suggested that DAP could have antidotal efficacy if continuously delivered. To test for antidotal capability, DAP was continuously infused at nontoxic levels in rats intoxicated with 2 LD50 of BoNT/A, starting after signs of botulism emerged. DAP enabled 100% survival, whereas saline‐treated rats died in 2.8 days. Infusion was stopped at two weeks once respiratory signs of botulism resolved, and rats remained healthy and active through study end at three weeks, without symptomatic rebound. Following euthanasia, electrophysiological characterization revealed a large fraction of phrenic endplates that continued to exhibit impaired neuromuscular transmission, despite the apparent absence of physiological signs of botulism. These data suggest that treatment with DAP allowed for the emergence of compensatory changes in neuromuscular function that promoted physiological recovery. Not only do the underlying mechanisms represent fertile ground for therapeutic exploitation, but they are also important for understanding regenerative responses following transient chemical denervation of the respiratory system.These studies indicate that DAP has unique potential to improve respiratory function during botulism. Furthermore, they demonstrate the first antidotal treatment of type A botulism in vivo. We are currently preparing to evaluate the effects of DAP on respiratory function and intensity and duration of supportive care in patients suffering natural and iatrogenic botulism.Support or Funding InformationThis project was funded by the Defense Threat Reduction Agency and NIH (R01A193504); and supported by appointments to the Postgraduate Research Participation Program at USAMRICD administered by the Oak Ridge Institute for Science and Education.

Highlights of serious distant effects after local injection of botulinum toxin therapy: A report of pediatric case

Introduction: Botulinum neurotoxin A (BoNT-A) is widely used in various conditions that cause involuntary muscle contractions, such as management of spasticity in cerebral palsy (CP). However, iatrogenic botulism resulting from systemic effects from BoNT-A is uncommon but may have serious life-threatening consequences. Case Report: We report a case of pediatric patient who developed iatrogenic botulism after therapeutic intramuscular injections of BoNT-A. Conclusion: This case highlights the importance of clinicians having adequate information of the risk of systemic botulism following local injections of BoNT-A and caution is needed in using this therapy.

Ботулинотерапия и ятрогенный ботулизм: взгляд инфекциониста на проблему

Ботулинотерапия и ятрогенный ботулизм: взгляд инфекциониста на проблему

Electrophysiologic abnormalities in iatrogenic botulism: 2 case reports

Electrophysiologic abnormalities in iatrogenic botulism: 2 case reports