High risk and low prevalence diseases: Botulism.

INTRODUCTION: Botulism is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of botulism, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Botulism is a neuromuscular disorder caused by toxin production of clostridium species bacteria and is a challenging diagnosis that mimics several other conditions. Children account for the majority of patients, with a foodborne source most common, followed by wound sources, typically from intravenous drug injection. Classically, patients with botulism develop bilateral cranial nerve palsies and symmetric, bilateral, descending paralysis. However, patients may initially present with vague symptomatology, such as weakness and dry mouth, which can make diagnosis challenging. A careful history elucidating exposures such as intravenous drug use or consumption of non-commercial canned products can help differentiate botulism from other disorders causing neuromuscular weakness. If suspected, the Centers for Disease Control should be notified to mobilize antitoxin for treatment as soon as the diagnosis is suspected even prior to confirmatory testing. Antibiotics should be avoided in these patients, as they can potentiate toxin release, unless there is a concomitant infection requiring antibiotic therapy. Patients with botulism can develop respiratory compromise requiring emergent airway management. Prolonged neuromuscular blockade from botulism will lead to a variety of symptoms that require comprehensive intensive care unit level care. CONCLUSION: An understanding of botulism and its many potential mimics can assist emergency clinicians in diagnosing and managing this deadly disease.

Foodborne botulism outbreak with potential new management options.

OBJECTIVES: To shed some light on a potential therapeutic modality that may facilitate resolution of botulism symptoms, namely 3,4-diaminopyridine (3,4-DAP). METHODS: In Riyadh, Saudi Arabia, we recently encountered a foodborne botulism outbreak that, luckily, was discovered early. In Prince Sultan Military Medical city, we admitted, during a period of approximately 3 weeks, 15 probable cases, 2 of which were excluded due to more likely alternative diagnoses. We report in this case series 13 highly suspected cases of botulism that we encountered during the outbreak. RESULTS: A total of 12 out of 13 patients required intensive care unit (ICU) admission, one of which required intubation. Symptoms included cranial nerve palsies, gastrointestinal symptoms, limb and respiratory muscle weakness. Patients showed clinical improvement when received botulinum antitoxin and 3,4-DAP if given early in the course of the disease. CONCLUSION: Early admisntration of 3,4-DAP may facilitate recovery and prevent disease progression. Larger prospective trials should be carried out to confirm that.

Electrophysiological abnormalities of the neuromuscular transmission in two patients with botulism-like syndrome following Botulinum-A muscle injections.

Botulinum neurotoxin serotype A (BoNT-A) has several therapeutic indications such as spasticity and dystonia. Although its use is generally considered safe, a systemic diffusion can lead to systemic complications, and a botulism-like syndrome can occur after intramuscular injections. Herein, two adult cases who developed general muscle weakness after a BoNT-A intramuscular injection are reported. Both presented with a progressive decrement on low-frequency (LF) repetitive nerve stimulation (RNS). It is suggested that a progressive decrement on LF-RNS in muscles distant from the injection site strongly supports the diagnosis of iatrogenic botulism.

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.

Validation of a clinical assay for botulinum neurotoxins through mass spectrometric detection.

Botulism is a paralytic disease due to the inhibition of acetylcholine exocytosis at the neuromuscular junction, which can be lethal if left untreated. Botulinum neurotoxins (BoNTs) are produced by some spore-forming Clostridium bacteria. The current confirmatory assay to test for BoNTs in clinical specimens is the gold-standard mouse bioassay. However, an Endopep-MS assay method has been developed to detect BoNTs in clinical samples using benchtop mass spectrometric detection. This work demonstrates the validation of the Endopep-MS method for clinical specimens with the intent of method distribution in public health laboratories. The Endopep-MS assay was validated by assessing the sensitivity, robustness, selectivity, specificity, and reproducibility. The limit of detection was found to be equivalent to or more sensitive than the mouse bioassay. Specificity studies determined no cross-reactivity between the different serotypes and no false positives from an exclusivity panel of culture supernatants of enteric disease organisms and non-toxigenic strains of Clostridium. Inter-serotype specificity testing with 19 BoNT subtypes was 100% concordant with the expected results, accurately determining the presence of the correct serotype and the absence of incorrect serotypes. Additionally, a panel of potential interfering substances was used to test selectivity. Finally, clinical studies included clinical specimen stability and reproducibility, which was found to be 99.9% from a multicenter evaluation study. The multicenter validation study also included a clinical validation study, which yielded a 99.4% correct determination rate. Use of the Endopep-MS method will improve the capacity and response time for laboratory confirmation of botulism in public health laboratories.

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.

[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.

Iatrogenic botulism. / Iatrogen botulisme.

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

Delayed onset post-traumatic wound botulism.

A 41-year-old man developed rapidly progressive cranial neuropathies and muscle weakness followed by respiratory failure, requiring ventilation support. On examination, there was marked bilateral ptosis and ophthalmoplegia with bulbar, neck and proximal upper limb weakness. He had a recent open left humeral fracture that eventually required amputation. Despite immunoglobulin therapy, his progressive weakness continued. Multiple investigation results were inconclusive. Eventually, botulinum type A toxin was found positive, by which time the therapeutic window for antitoxin had passed. He continued on supportive management and was treated for concomitant infections and nosocomial illnesses. He was subsequently weaned from respiratory support and has made a good neurological recovery.

An outbreak of type C botulism in free-ranging Southern lapwing (Vanellus chilensis).

In the fall of 2021, a significant mortality event in free-ranging Southern Lapwing (Vanellus chilensis) occurred on a soccer field in southern Brazil. Approximately 130 adult southern lapwings died after showing weakness and flaccid paralysis, characterized by the inability to move or fly and drooped wings. Due to the large number of animals affected, there was concern that they had been criminally poisoned. The affected birds were found to have ingested maggots in fresh poultry litter incorporated into the grass surface. Postmortem examinations of four southern lapwings revealed no significant gross and histological findings. Polymerase Chain Reaction (PCR) for influenza A virus, flavivirus, and paramyxovirus was negative. Based on the epidemiological and clinical findings and the negative viral results, a presumptive diagnosis of botulism was made. This diagnosis was confirmed through mouse bioassay and seroneutralization, which detected botulinum toxin type C. Maggots loaded with botulinum neurotoxins were the probable vehicle for intoxication in the outbreak. Considering the impact of avian botulism on wild bird populations, our results may help prevent similar outbreaks in the future.

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 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.

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.

Postprandial hypotension as a predictor of respiratory failure in patients with foodborne botulinum intoxication - a case-control study in outbreak investigation.

OBJECTIVES: Botulism is a rare syndrome characterized by acute, flaccid paralysis with possible involvement of respiratory muscle-producing pump failure requiring mechanical ventilation. A predominance of autonomic involvement can occur. METHODS: We enrolled patients affected by foodborne botulism during an outbreak. All patients underwent the detection of the toxin in stool specimens, and 24-hour ambulatory blood pressure monitoring (ABPM). A blinded expert operator analyzed ABPM data for the diagnosis of hypertension and postprandial hypotension (PPH). RESULTS: Twenty male patients met the inclusion and exclusion criteria. Thirty-four healthy subjects matched for sex and age were enrolled as a control group. PPH was significantly more frequent in the botulin group than in healthy subjects (40% vs 2.9%, P <0.0001). At the logistic regression, the probability that patients affected by botulinum could require ventilation was increased by 733% (adjusted odds ratio: 8.33) when PPH is encountered. CONCLUSIONS: The likelihood of resorting to ventilation in subjects with botulinum intoxication was seven times greater in patients presenting PPH. These results could allow the prompt identification of patients at high risk for requiring ventilation.

Septic shock due to Clostridium botulinum: a case report.

BACKGROUND: Clostridium botulinum is an anaerobic, Gram-positive, rod-shaped bacterium that forms spores and the neurotoxin botulinum. It is best known for its toxin-induced flaccid paralytic disease, which is deadly without correct treatment. In this report, we show a completely different clinical course with fatal outcome. CASE PRESENTATION: A 37-year-old African man born in Sierra Leone was admitted. After admission, his condition rapidly worsened due to severe septic shock and progressive multiorgan failure. No neurological signs were seen. Despite treatment with antibiotics, fluid resuscitation, and norepinephrine, the multiorgan failure deteriorated further and he died as a result. Blood and synovial fluid cultures showed Clostridium botulinum. No botulinum toxins were found. CONCLUSION: This is a rare case of fatal septic shock due to Clostridium botulinum-induced septic arthritis without any sign of the classic clinical syndrome of botulism.

Foodborne Botulism, Canada, 2006-20211.

During 2006-2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous communities accounted for 46% of all cases, which is down from 85% of all cases during 1990-2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.

[A case of botulism in the Czech Republic and current possibilities for detecting the neurotoxin produced by Clostridium botulinum].

In the Czech Republic, botulism is a rare life-threatening disease. A total of 155 cases have been reported since 1960; according to the ISIN (formerly EPIDAT) database, there have been only three isolated cases since 2013, with the exception of a single occurrence of familial botulism in 2013. In our work, we present the occurrence of botulism after ingestion of pâté of untraceable origin by a couple who were hospitalized for botulotoxin food poisoning in July 2022. Their neurological symptoms were dominated by dysarthria. After administration of antibotulinum serum, their condition improved significantly. Patient samples were analyzed using affinity carriers and MALDI mass spectrometry, a modern highly sensitive technique for detecting the presence of botulinum neurotoxins. Unlike traditional detection by a difficult and costly biological experiment on mice, the above analysis does not require the killing of laboratory animals.

Botulism mimicking Guillain-Barre syndrome: The question of plasma exchange in an unusual case of acute paralysis.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide. GBS classically presents with acute, progressive, ascending weakness, reduced to absent reflexes, and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis. Botulism is a neurotoxin-mediated acute descending flaccid paralysis with cranial nerve palsies and dysautonomia. Botulism in adults is caused by ingestion/inhalation of botulinum toxin or wound infection with Clostridium botulinum. Both GBS and botulism can rapidly precipitate respiratory failure; thus, prompt diagnosis and treatment are crucial to mitigate poor outcomes. Herein, we describe a case of botulism initially diagnosed as GBS given classic laboratory features, and describe the importance of careful consideration of the most appropriate therapeutic modalities in cases of acute flaccid paralysis, particularly regarding empiric administration of botulinum antitoxin and use of intravenous immune globulin in lieu of plasma exchange for potential GBS to prevent removal of antitoxin.