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.

Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.

BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

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 Beauty to Botulism: A Case Report Highlighting the Rare Risk of Botox Administration.

Botox (onabotulinumtoxinA) is a pharmaceutical approved by the Food and Drug Administration (FDA) for use in both cosmetic and therapeutic applications. Despite its increasing use worldwide, Botox carries a rare but potentially life-threatening risk of iatrogenic botulism. This condition, although treatable with antitoxin if promptly recognized, presents a diagnostic challenge to healthcare providers due to its rarity, lack of awareness, and diverse clinical presentations. Here, we present a case of iatrogenic botulism from Botox injections administered in Istanbul, Turkey, in a healthy 47-year-old female. Prompt administration of antitoxin led to remarkable clinical improvement. This case underscores the importance of vigilance among healthcare providers in recognizing and promptly treating iatrogenic botulism, particularly in patients with recent Botox use. Given that the majority of reported cases of iatrogenic botulism occur outside the United States, this case raises concerns about the need for stricter regulations and oversight of Botox administration worldwide.

Botulism in fish: a review.

Published information about fish botulism is scant. We review here the current literature on fish botulism. Freshwater fish are susceptible to botulism. Only anecdotal evidence exists about possible botulism cases in saltwater fish. With only a few exceptions, the etiology of all cases of fish botulism reported is Clostridium botulinum type E, although fish are sensitive to, and may carry, various C. botulinum types. Clinical signs of botulism in fish include loss of equilibrium and motion, abducted opercula, open mouths, dark pigmentation, and head up/tail down orientation in which attempts to swim result in breaching the surface of the water. Dark pigmentation is thought to be associated with acetylcholine imbalance in botulinum neurotoxin (BoNT)-affected fish. Rarely, but similar to the situation in other animal species, fish can recover from botulism. Fish botulism can cause secondary outbreaks of the disease in birds, as botulism-affected fish stand out from normal fish, and are selectively preyed upon by fish-eating birds, which thus become intoxicated by the BoNT present in sick fish. The source of BoNT in fish has not been definitively confirmed. Fish may ingest C. botulinum spores that then germinate in their digestive tract, but the possibility that fish ingest preformed BoNT from the environment (e.g., dead fish, shellfish, insects) cannot be ruled out. The presumptive diagnosis of botulism in fish is established based on clinical signs, and as in other species, confirmation should be based on detection of BoNT in intestinal content, liver, and/or serum of affected fish.

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.

Equine grass sickness is associated with major abnormalities in the ultrastructure of skeletal neuromuscular junctions.

BACKGROUND: Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown. OBJECTIVES: To compare the organisation and structural integrity of skeletal NMJs from EGS horses, control horses and one horse with a presumptive diagnosis of botulism. STUDY DESIGN: Blinded, retrospective case control. METHODS: NMJs in samples of diaphragm or intercostal muscle from six EGS horses, three control horses and one equine botulism case were compared using electron microscopy, morphometry and confocal light microscopy. RESULTS: A significantly higher percentage of EGS NMJs had abnormal morphology (EGS 72.2%, 95% CI 55.6-84.4; Controls 6.9%, 1.7-23.8; OR 35.1, 8.47-244.8; p < 0.001). EGS NMJs had a significantly lower mean volume fraction occupied by synaptic vesicles (SVs) (EGS 18.7%, 12.6-28.0; Controls 36.3%, 20.8-63.4; p = 0.024). EGS NMJs had evidence of accelerated SV exocytosis and SV depletion, accumulation of neurofilament-like material in terminal boutons and/or bouton degeneration. NMJs from the botulism horse had dense packing of SVs towards the presynaptic membrane active zone, consistent with BoNT intoxication, but had absence of the abnormalities identified in EGS NMJs. MAIN LIMITATIONS: Group sizes were limited by difficulties obtaining suitably processed samples. Ages of control and EGS horses differed. Botulism was diagnosed based on clinical and post mortem findings. CONCLUSIONS: EGS is associated with major changes in skeletal NMJ ultrastructure that are inconsistent with the effects of BoNTs. SV depletion may reflect increased exocytosis coupled with reduced repopulation of SVs via anterograde axonal transport and endocytosis, consistent with the action of an excitatory presynaptic toxin and/or neurotransmitter reuptake inhibitor. Skeletal NMJs represent a previously unrecognised target for the toxin that causes EGS.

That head lag is impressive! Infantile botulism in the NICU: a case report.

BACKGROUND: Infantile botulism (IB) is a devastating and potentially life-threatening neuromuscular disorder resulting from intestinal colonization by Clostridium botulinum and the resultant toxin production. It can present with constipation, descending paralysis, and, potentially, respiratory failure. Botulism is a diagnosis that is more commonly seen in the pediatric intensive care unit (PICU) or on the general pediatric wards and would not typically be managed in the neonatal intensive care unit (NICU), and therefore requires high clinical suspicion to ensure prompt diagnosis and treatment. CASE PRESENTATION: We discuss a case where an infant from central Pennsylvania presented to a Level IV NICU rather than to the PICU for an evaluation for sepsis and was uniquely diagnosed with IB. The infant presented with poor oral feeding and reduced oral intake, hypothermia, and lethargy. His symptoms progressed into hypoxia and acute respiratory failure. Interestingly, this infant had no known exposure to honey or any other identifiable sources of botulism contact. The infant's twin brother and the other infants who attended the mother's in-home daycare remained asymptomatic. This infant was initially evaluated and managed for a potential infectious etiology. However, a diagnosis of IB was suspected, and was later confirmed through the detection of botulinum toxin in the infant's stools. A high level of suspicion allowed for timely treatment with Botulism Immune Globulin neutralizing antibodies (BabyBIG), even prior to confirmatory testing. We describe the process of obtaining BabyBIG, as well as the natural course of illness after treatment in our patient who ultimately made a complete recovery. CONCLUSIONS: This case highlights the importance of considering infantile botulism as a diagnostic possibility even in the absence of risk factors, and the need for vigilance in diagnosing and treating this rare but potentially life-threatening condition. With timely recognition, subsequent treatment with BabyBIG, and supportive care, infants with infantile botulism can be expected to recover completely. This information is particularly important for neonatologists providing care for infants outside the neonatal period, especially during times of high patient census and resulting overflow of pediatric admissions in the NICU.

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.

Closed genome sequence of Clostridium botulinum type B1 strain isolated from an infant botulism case in the United States.

We present the closed genome sequence of the Clostridium botulinum BT-22100019 strain isolated from the stool specimen of an infant diagnosed with botulism. With 4.33-Mb genome size and 28.0% G + C content, the bont/B1 gene encoded for botulinum neurotoxin serotype B was found on a 262 kb plasmid arranged in a ha+ orfx - cluster.

The Latent Threat in Wild Birds: Clostridium botulinum.

Avian botulism caused by Clostridium botulinum emerged in 1910, affecting birds across North America, leading to severe outbreaks exacerbated by climate change, decreasing water levels, and inadequate wastewater management. While deadly for birds, its epidemiological impact on humans and other animals remains limited. Despite its significance, understanding and controlling the disease remain challenging. This review delves into the pathogen's epidemiology in wild bird populations, exploring the transmission, pathogenicity, clinical symptoms, diagnosis and treatment. The disease's growing concern in wild birds relates to the bacterium's adaptability and expansive spread, evident through genetic similarities among strains across countries. Outbreaks are influenced by environmental factors such as temperature and soil characteristics. Wild birds inadvertently transmit the bacterium, perpetuating the cycle through carcasses and flies. Some species suffer severely, while others, like scavengers, show resistance. Understanding disease mechanisms, involving potential toxin ingestion or internal production, remains ongoing. Clinical signs vary, affecting diverse bird orders. Diagnostic methods evolve, with treatment success varying among affected populations. Prevention and surveillance take precedence due to treatment challenges, emphasising population-based strategies and preventive measures to manage the widespread presence of C. botulinum.

NTNH protein: more than a bodyguard for botulinum neurotoxins.

As one of the most fatal substances, botulinum neurotoxins (BoNTs) have never acted solo to accomplish their formidable missions. Most notably, nontoxic nonhemagglutinin (NTNH), a protein co-secreted with BoNT by bacteria, plays critical roles to stabilize and protect BoNT by tightly associating with it to form the minimal progenitor toxin complex (M-PTC). A new cryo-EM structure of the M-PTC of a BoNT-like toxin from Weissella oryzae (BoNT/Wo) reveals similar assembly modes between M-PTC/Wo and that of other BoNTs, yet also reveals some unique structural features of NTNH/Wo. These findings shed new light on the potential versatile roles of NTNH during BoNT intoxication.

Rare Case of Botulism and Dysphagia: The Role of Physical and Rehabilitation Medicine.

Botulism is a rare cause of flaccid paralysis resulting from the neurotoxin produced by the bacterium Clostridium botulinum. It is clinically characterized by symmetric proximal-distal paralysis, diplopia, dysarthria, dysphonia, and dysphagia. Definitive diagnosis requires laboratory confirmation through the detection of the toxin in blood, vomit, or stool samples. Treatment with antitoxin should be promptly initiated upon clinical suspicion and in the presence of epidemiological support due to evidence of reduced mortality. Physical and rehabilitation medicine plays a fundamental role in the recovery of deficits and prevention of complications. In this report, the authors describe a 19-year-old patient with botulism with dysphagia, dysphonia, and facial paresis in the rehabilitation ward.

Clinicopathological insights into an outbreak of foodborne botulism in Hamadan, Iran, in 2023: A microbiological and laboratory findings.

Background and Objective: Foodborne botulism is one of the potentially fatal forms of food poisoning, usually caused by ingestion of home-canned vegetables, fruits, and dairy and fish products. This study aimed to assess the frequency of signs and symptoms in patients with botulism following the ingestion of homemade Doogh, a traditional milk-based beverage, in Hamadan, Iran in 2023. We also examined the general characteristics of the recruited patients. Methods: During an outbreak, 21 patients were referred to the hospital because of food poisoning. All patients had a history of consumption of Doogh. After careful physical examination, all of them were hospitalized. Botulism was suspected in all patients except for the first patient. Results: The mean age of admitted patients was 33.09 ± 18.44 years, with 23.80% being males and 76.20% females. Incubation period in our patients was 68 ± 28.48 h. Notable symptoms included diplopia (95.23%), nausea and vomiting (85.71%), blurred vision (80.95%), and dizziness (61.90%). The laboratory results were within the normal range. No deaths occurred in this patient cohort. Furthermore, botulinum spores were detected in Doogh samples collected from the outbreak, confirming the presence of Clostridium botulinum spores as a source of the outbreak. Conclusions: This study highlights that the initial manifestations of botulism predominantly involved ophthalmologic abnormalities in most patients. Additionally, symptoms such as nausea, vomiting, and dizziness may manifest in cases of foodborne botulism. Timely diagnosis and treatment of botulism following the consumption of homemade Doogh played a crucial role in achieving positive outcomes, with no fatalities recorded in this patient cohort.

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.

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.

Food-borne botulism from homemade sauce leading to cardiac arrest: A family case series with literature review.

Food-borne botulism is a rare but potentially fatal illness. Its management depends on rapid diagnosis and prompt antitoxin administration. However, diagnosing food-borne botulism can be challenging at an early stage. Here, we report a 62-year-old male with food-borne botulism. The patient presented with extremity muscle weakness, dyspnea, bilateral droopy eyelids (more significant on the right side), dysarthria, and progressive dysphagia. The electromyography indicated presynaptic membrane abnormalities. The toxicology screen reported a positive result for botulinum toxin type A. He received plasma exchange, botulism antitoxin, and supportive care. However, he had a cardiac arrest six days later. Spontaneous circulation was restored after immediate cardiopulmonary resuscitation. The patient gradually recovered his muscle strength and could have complete eyelid elevation. A detailed interview revealed that six family members developed similar symptoms. All of them consumed a homemade sauce prepared three years ago. They all tested positive for botulinum toxin type A. Two of them had cardiac arrests. Therefore, family aggregation could happen to botulism. Careful interviews, early diagnosis, and timely administration of botulism antitoxin are the keys to saving lives. Special attentions should be given to the cardiac evaluations since botulism can cause cardiac arrest and death.

Food-borne botulism outbreak during the Rugby World Cup linked to marinated sardines in Bordeaux, France, September 2023.

In September 2023, a botulism outbreak affecting 15 individuals occurred in Bordeaux, France, during the Rugby World Cup. We report on eight individuals from four different countries on two continents admitted to the intensive care unit at our hospital, where six required invasive mechanical ventilation. Cases reported consuming locally produced canned sardines at a restaurant. This report highlights the importance of rapid, worldwide alerts from health authorities to prevent severe consequences of such outbreaks, particularly during events attracting international visitors.