Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

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.

Production of monoclonal antibodies against botulinum neurotoxin in Nicotiana benthamiana.

Botulism is a fatal neurologic disease caused by the botulinum toxin (BoNT) produced by Clostridium botulinum. It is a rare but highly toxic disease with symptoms, such as cramps, nausea, vomiting, diarrhea, dysphagia, respiratory failure, muscle weakness, and even death. Currently, two types of antitoxin are used: equine-derived heptavalent antitoxin and human-derived immunoglobulin (BabyBIG®). However, heptavalent treatment may result in hypersensitivity, whereas BabyBIG®, has a low yield. The present study focused on the development of three anti-BoNT monoclonal antibodies (mAbs), 1B18, C25, and M2, in Nicotiana benthamiana. The plant-expressed mAbs were purified and examined for size, purity and integrity by SDS-PAGE, western blotting and size-exclusion chromatography. Analysis showed that plant-produced anti-BoNT mAbs can fully assemble in plants, can be purified in a single purification step, and mostly remain as monomeric proteins. The efficiency of anti-BoNT mAbs binding to BoNT/A and B was then tested. Plant-produced 1B18 retained its ability to recognize both mBoNT/A1 and ciBoNT/B1. At the same time, the binding specificities of two other mAbs were determined: C25 for mBoNT/A1 and M2 for ciBoNT/B1. In conclusion, our results confirm the use of plants as an alternative platform for the production of anti-BoNT mAbs. This plant-based technology will serve as a versatile system for the development botulism immunotherapeutics.

From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction.

Since its regulatory approval over a half-century ago, botulinum toxin has evolved from one of the most potent neurotoxins known to becoming routinely adopted in clinical practice. Botulinum toxin, a highly potent neurotoxin produced by Clostridium botulinum, can cause botulism illness, characterized by widespread muscle weakness due to inhibition of acetylcholine transmission at neuromuscular junctions. The observation of botulinum toxin's anticholinergic properties led to the investigation of its potential benefits for conditions with an underlying etiology of cholinergic transmission, including autonomic nervous system dysfunction. These conditions range from disorders of the integument to gastrointestinal and urinary systems. Several formulations of botulinum toxin have been developed and tested over time, significantly increasing the availability of this treatment for appropriate clinical use. Despite the accelerated and expanded use of botulinum toxin, there lacks an updated comprehensive review on its therapeutic use, particularly to treat autonomic dysfunction. This narrative review provides an overview of the effect of botulinum toxin in the treatment of autonomic dysfunction and summarizes the different formulations and dosages most widely studied, while highlighting reported outcomes and the occurrence of any adverse events.

Evaluation of long-term immune response in cattle to botulism using a recombinant E. coli bacterin formulated with Montanide™ ISA 50 and aluminum hydroxide adjuvants.

Botulism is a severe disease caused by potent botulinum neurotoxins (BoNTs) produced by Clostridium botulinum. This disease is associated with high-lethality outbreaks in cattle, which have been linked to the ingestion of preformed BoNT serotypes C and D, emphasizing the need for effective vaccines. The potency of current commercial toxoids (formaldehyde-inactivated BoNTs) is assured through tests in guinea pigs according to government regulatory guidelines, but their short-term immunity raises concerns. Recombinant vaccines containing the receptor-binding domain have demonstrated potential for eliciting robust protective immunity. Previous studies have demonstrated the safety and effectiveness of recombinant E. coli bacterin, eliciting high titers of neutralizing antibodies against C. botulinum and C. perfringens in target animal species. In this study, neutralizing antibody titers in cattle and the long-term immune response against BoNT/C and D were used to assess the efficacy of the oil-based adjuvant compared with that of the aluminum hydroxide adjuvant in cattle. The vaccine formulation containing Montanide™ ISA 50 yielded significantly higher titers of neutralizing antibody against BoNT/C and D (8.64 IU/mL and 9.6 IU/mL, respectively) and induced an immune response that lasted longer than the response induced by aluminum, extending between 30 and 60 days. This approach represents a straightforward, cost-effective strategy for recombinant E. coli bacterin, enhancing both the magnitude and duration of the immune response to botulism.

Iatrogenic botulism. / Iatrogen botulisme.

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

[Clinical characteristics and prognosis of 8 cases of severe infant botulism].

Objective: To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU). Methods: The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children's Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods. Results: Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering. Conclusions: For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Botulinum neurotoxin X lacks potency in mice and in human neurons.

Botulinum neurotoxins (BoNTs) are a class of toxins produced by Clostridium botulinum (C. botulinum) and other species of Clostridia. BoNT/X is a putative novel botulinum neurotoxin identified through genome sequencing and capable of SNARE cleavage, but its neurotoxic potential in humans and vertebrates remained unclear. The C. botulinum strain producing BoNT/X, Strain 111, encodes both a plasmid-borne bont/b2 as well as the chromosomal putative bont/x. This study utilized C. botulinum Strain 111 from Japan as well as recombinantly produced full-length BoNT/X to more fully analyze this putative pathogenic toxin. We confirmed production of full-length, catalytically active native BoNT/X by C. botulinum Strain 111, produced as a disulfide-bonded dichain polypeptide similar to other BoNTs. Both the purified native and the recombinant BoNT/X had high enzymatic activity in vitro but displayed very low potency in human-induced pluripotent stem cell-derived neuronal cells and in mice. Intraperitoneal injection of up to 50 µg of native BoNT/X in mice did not result in botulism; however, mild local paralysis was observed after injection of 2 µg into the gastrocnemius muscle. We further demonstrate that the lack of toxicity by BoNT/X is due to inefficient neuronal cell association and entry, which can be rescued by replacing the receptor binding domain of BoNT/X with that of BoNT/A. These data demonstrate that BoNT/X is not a potent vertebrate neurotoxin like the classical seven serotypes of BoNTs. IMPORTANCE: The family of botulinum neurotoxins comprises the most potent toxins known to humankind. New members of this family of protein toxins as well as more distantly related homologs are being identified. The discovery of BoNT/X via bioinformatic screen in 2017 as a putative new BoNT serotype raised concern about its potential as a pathogenic agent with no available countermeasures. This study for the first time assessed both recombinantly produced and native purified BoNT/X for its vertebrate neurotoxicity.

Non-invasive diagnosis of diaphragmatic paralysis in botulism using ultrasound.

This case study explores foodborne botulism, a severe illness caused by botulinum neurotoxin-contaminated food. It leads to bilateral descending paralysis, involving the diaphragm. We highlight diaphragmatic ultrasound as a non-invasive diagnostic tool. A 50-year-old obese male developed diplopia and weakness after consuming contaminated food, rapidly progressing to severe symptoms. Mechanical ventilation became necessary due to respiratory failure. Diaphragmatic ultrasound confirmed bilateral diaphragm paralysis despite early antitoxin treatment. The patient experienced complications, requiring tracheostomy and rehabilitation. After five months, he fully recovered diaphragmatic function. This study underscores botulism's life-threatening nature and the vital role of supportive care. Diaphragmatic ultrasound is a safe and effective method for assessing diaphragmatic function in such cases, obviating ionizing radiation exposure. We recommend its routine use for evaluating botulism-induced paralysis.

Complete genomes of Clostridium botulinum type B(F) isolates associated with a 1995 foodborne botulism outbreak from commercial pâté reveals a recombination event disrupting the ntnh gene.

Foodborne botulism is a neuroparalytic disease caused by ingestion of foods contaminated with botulinum neurotoxin (BoNT), produced by Clostridium botulinum. In 1995 a husband and wife from Québec, Canada, were hospitalized for several months with prolonged muscle paralysis after ingesting a commercial pâté de campagne. Examination of faecal samples from both patients and the pâté produced viable Group I (proteolytic) C. botulinum type B from each of the three samples. Whole genome sequencing revealed that all three isolates contain identical bont/B5 and bont/F2 genes encoded on a plasmid. Both faecal isolate genomes were identical in chromosome and plasmid length, as well as gene content. The genome of the pâté isolate was nearly identical to that of the faecal isolates with the notable difference of a missing 13-gene insertion on the bont/B5 cluster disrupting the ntnh gene. Examination of the insertion revealed several mobile genetic elements that participate in recombination.

Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.

Botulism in Two Juvenile Wild Red Foxes (Vulpes vulpes) in Somerset, England, UK.

Two juvenile red foxes (Vulpes vulpes) were euthanased because of severe nervous signs and paralysis. Detailed postmortem examinations were carried out with bacteriology, histology, and Clostridium botulinum toxin screening, which confirmed botulism as the cause of the clinical signs.

Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.

Botulinum neurotoxin (BoNT) is a potent protein toxin that causes muscle paralysis and death by asphyxiation. Treatments for symptomatic botulism are intubation and supportive care until respiratory function recovers. Aminopyridines have recently emerged as potential treatments for botulism. The clinically approved drug 3,4-diaminopyridine (3,4-DAP) rapidly reverses toxic signs of botulism and has antidotal effects when continuously administered in rodent models of lethal botulism. Although the therapeutic effects of 3,4-DAP likely result from the reversal of diaphragm paralysis, the corresponding effects on respiratory physiology are not understood. Here, we combined unrestrained whole-body plethysmography (UWBP) with arterial blood gas measurements to study the effects of 3,4-DAP, and other aminopyridines, on ventilation and respiration at terminal stages of botulism in mice. Treatment with clinically relevant doses of 3,4-DAP restored ventilation in a dose-dependent manner, producing significant improvements in ventilatory parameters within 10 minutes. Concomitant with improved ventilation, 3,4-DAP treatment reversed botulism-induced respiratory acidosis, restoring blood levels of CO2, pH, and lactate to normal physiologic levels. Having established that 3,4-DAP-mediated improvements in ventilation were directly correlated with improved respiration, we used UWBP to quantitatively evaluate nine additional aminopyridines in BoNT/A-intoxicated mice. Multiple aminopyridines were identified with comparable or enhanced therapeutic efficacies compared with 3,4-DAP, including aminopyridines that selectively improved tidal volume versus respiratory rate and vice versa. In addition to contributing to a growing body of evidence supporting the use of aminopyridines to treat clinical botulism, these data lay the groundwork for the development of aminopyridine derivatives with improved pharmacological properties. SIGNIFICANCE STATEMENT: There is a critical need for fast-acting treatments to reverse respiratory paralysis in patients with botulism. This study used unrestrained, whole-body plethysmography and arterial blood gas analysis to show that aminopyridines rapidly restore ventilation and respiration and reverse respiratory acidosis when administered to mice at terminal stages of botulism. In addition to supporting the use of aminopyridines as first-line treatments for botulism symptoms, these data are expected to contribute to the development of new aminopyridine derivatives with improved pharmacological properties.

Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta-analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. METHODS: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. RESULTS: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self-limiting. CONCLUSION: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long-term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911).

Standardization of the Japanese National Standard, Equine Botulinum Antitoxin Type A, and Factors Affecting Standardization.

Equine botulinum antitoxin is one of the most popular countermeasures for human botulism. The unitage of the antitoxin product is defined according to national minimum requirement or pharmacopoeia in each country by referring to national standard antitoxins for four types (A, B, E, and F). With the expected depletion of the national standard antitoxins, replacement national standard antitoxins are produced and standardized through collaboration of the National Control Laboratory and other participants, including manufacturer(s). Therefore, Japanese National Standard Botulinum Antitoxin Type A, Equine, was replaced according to the results of a collaborative study involving the National Institute of Infectious Diseases and KM Biologics Co., Ltd. The unitage of the replacement material was determined through mouse neutralization tests, which involved toxin-antitoxin mixture injection at pH 7.0. Potency value of 440 units/vial was obtained. However, the Japanese Minimum Requirement for Biological Products was revised, and the neutralization reactions were repeated at pH 6.0, for which considerably different potency value (656 units/vial) and survival profile of mice were obtained. In September 2021, the replacement material, Japanese National Standard Botulinum Antitoxin Type A, Equine, lot 2, was established with potency value of 656 Units/vial. The impact of pH-dependent change in potency on antitoxin quality control is discussed.

Electrophysiological evaluation of the neuromuscular junction: a brief review.

The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ("jiggle") due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.

O nervo terminal e a membrana muscular compõem a junção neuromuscular. Após a abertura dos canais de cálcio dependentes de voltagem, os potenciais de ação do axônio motor provocam uma cascata de eventos que libera acetilcolina das vesículas para a fenda sináptica, ligando-se ao receptor na membrana muscular para despolarização. O potencial de ação muscular composto de baixa amplitude ocorre nas desordens pré-sinápticas, aumentando em mais de 100% após esforço de 10 segundos na síndrome miastênica de Lambert-Eaton e menos no botulismo. A eletromiografia pode mostrar potenciais de ação da unidade motora miopáticos e instabilidade morfológica ("jiggle") devido ao bloqueio do impulso. Estimulação nervosa repetitiva (ENR) de baixa frequência é útil nos distúrbios pós-sinápticos, como miastenia gravis e a maioria das síndromes miastênicas congênitas, quando há número reduzido de receptores de acetilcolina funcionantes. ENR de baixa frequência com decremento >10% é anormal comparando-se à amplitude do quarto com o primeiro potencial de ação muscular composto. ENR de alta frequência é útil nas doenças pré-sinápticas, como síndrome miastênica de Lambert-Eaton, botulismo e algumas síndromes miastênicas congênitas raras. ENR de alta frequência libera mais cálcio, aumenta acetilcolina, resultando em incremento do potencial de ação muscular composto. O eletrodo de agulha concêntrico registra potenciais de ação aparente de fibra única (PAAFU). Ativação voluntária mede jitter entre dois PAAFUs (duas junções neuromusculares). Ativação elétrica mede jitter de um PAAFU (uma junção neuromuscular). Jitter é o teste mais sensível para detectar disfunção de junção neuromuscular. A maioria dos distúrbios juncionais é responsiva ao tratamento.

Foodborne botulism outbreak involving different nationalities during the Rugby World Cup: critical role of credit card data and rapid international cooperation, France, September 2023.

In September 2023, a severe outbreak of type B botulism with fifteen cases was linked to consumption of canned sardines at a restaurant in Bordeaux, France, during the Rugby World Cup. The cases were from seven countries. One death was recorded. Outbreak investigation using credit card data, rapid communication between health authorities of the affected countries and broad media communication allowed identification of cases and exposed persons and prevented further severe outcomes.

Knowledge, attitude and practice among mothers on the relationship between honey and botulism in Saudi Arabian infants: a cross-section study.

BACKGROUND: Botulism is a rare disease, and infant botulism (IB) even rarer, especially when steering the condition to honey consumption. IB is considered a life-threatening disease as it leads to severe neurological symptoms. Exploring the knowledge, attitude, and practice (KAP) among mothers on the relationship between honey and IB will help public health professionals implement appropriate maternal health education materials targeting infant health and increase the awareness of the paediatric primary care providers, physicians, and nurse practitioners about the risk of IB among their patients. OBJECTIVES: To determine the knowledge of mothers from Hail city in Saudi Arabia (SA) regarding IB and assess their attitude and practice towards feeding honey to their infants before 12 months of age. METHODS: Using a comparative cross-sectional study, in February 2022, we broadcasted an online questionnaire through social networking and evaluated the KAP of 385 mothers. RESULTS: Less than half (48%) of the mothers have heard about IB, 40% of them knew the relation between honey ingestion and IB and only 6.5% acknowledged that they knew the causative agent for IB. The prevalence of feeding honey to infants before 12 months was 52%. Mothers from Hail city were less likely to provide honey to their infants (p = 0.002). CONCLUSION: The study revealed that mothers from Hail city have relatively low knowledge of IB and that they hold favourable perceptions of using honey as a food supplement and feeding honey to their infants before 12 months. Considering the high prevalence of honey feeding with the known low incidence of IB in SA, Medical professionals should consider IB in their differential diagnosis particularly in the presence of neurological symptoms.

A human bispecific antibody neutralizes botulinum neurotoxin serotype A.

Botulinum neurotoxin (BoNT) shows high lethality and toxicity, marking it as an important biological threat. The only effective post-exposure therapy is botulinum antitoxin; however, such products have great potential for improvement. To prevent or treat BoNT, monoclonal antibodies (mAbs) are promising agents. Herein, we aimed to construct a bispecific antibody (termed LUZ-A1-A3) based on the anti-BoNT/A human monoclonal antibodies (HMAb) A1 and A3. LUZ-A1-A3 binds to the Hc and L-HN domains of BoNT/A, displaying potent neutralization activity against BoNT/A (124 × higher than that of HMAb A1 or HMAb A3 alone and 15 × higher than that of the A1 + A3 combination). LUZ-A1-A3 provided effective protection against BoNT/A in an in vivo mouse model. Mice were protected from infection with 500 × LD50 of BoNT/A by LUZ-A1-A3 from up to 7 days before intraperitoneal administration of BoNT/A. We also demonstrated the effective therapeutic capacity of LUZ-A1-A3 against BoNT/A in a mouse model. LUZ-A1-A3 (5 µg/mouse) neutralized 20 × LD50 of BoNT/A at 3 h after intraperitoneal BoNT/A administration and complete neutralized 20 × LD50 of BoNT/A at 0.5 h after intraperitoneal BoNT/A administration. Thus, LUZ-A1-A3 is a promising agent for the pre-exposure prophylaxis and post-exposure treatment of BoNT/A.

Foodborne botulism in Poland in 2018-2021.

Objectives: The aim of this study is to assess the epidemiological situation of foodborne botulism in Poland in 2018-2021, compared to previous years. Materials and methods: The assessment is based on an analysis of aggregated surveillance data from the annual bulletin "Infectious Diseases and Poisons in Poland" from 2013-2021, as well as botulism case reports collected by sanitary-epidemiological stations and sent to the Department of Epidemiology of Infectious Diseases and Surveillance of the NIPH NIH - NRI or provided by EpiBase. Results: A total of 54 foodborne botulism cases were registered between 2018 and 2021, including 31 (57.4%) cases of laboratory-confirmed botulism intoxication. Most cases (46 cases, 85.2%) were sporadic. The declining trend in the number of notifications continued throughout the time period, and the incidence recorded in 2021 (0.02 per 100,000 population) was the lowest since the introduction of mandatory reporting and registration of botulism in Poland. The highest median annual incidence was recorded in the Warmisko-Mazurskie (0.18), but many voivodeships reported only single notifications or none. The decreasing trend in rural areas relative to the level of incidence in urban areas continued. Men (incidence in men more than twice that of women) and people aged 50-59 predominated. All patients were hospitalized. According to the State Sanitary Inspection, there were 3 deaths (mortality of 5.6%). Conclusions: In 2018-2021, the downward trend in the number of foodborne botulism notifications in Poland continued. At the same time, the considerable proportion of cases reported by physicians without laboratory confirmation and not meeting the definition of botulism adopted in other EU countries is noteworthy. The incidence in rural areas decreases to the level of incidence in urban areas, and the previously observed geographical distribution of cases diminishes.