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Background: Botulism is a rare and life-threatening disease caused by the potent botulinum neurotoxin (BoNT), which can be produced by Clostridium botulinum (C. botulinum) and related bacteria. Clinical manifestations, which include a symmetrical, descending muscular paralysis, generalized hypotonia, and potentially respiratory failure, are non-specific and diagnosis is challenging, especially when anamnesis does not reveal any typical risk factor, like honey consumption. Case Presentation: We present what is, to the best of our knowledge, the first documented case of infant botulism (IB) in Sicily and discuss its peculiarities and the challenges faced in the diagnostic-therapeutic process. The infant was exclusively breastfed and no history of consumption of possibly contaminated foods, like honey, was found. The signs observed at presentation included poor suction, hypotonia, and hyporeactivity. A detailed anamnesis motivated the suspicion of botulism, due to the occurrence of constipation and exposure to dust from home renovation works during the days before the onset of symptoms. The botulinum antitoxin was administered and the diagnosis was confirmed through fecal examination, detecting toxin-producing C. botulinum. Conclusion: IB should be considered in every infant with rapidly progressing hypotonia and a history of constipation. However rarely, transmission could occur through inhalation of dust particles containing the toxin, therefore it is important to explore all possible sources of exposure. In the case described, timely diagnosis and treatment determined the successful outcome, which highlights the importance of early intervention in managing IB. [ABSTRACT FROM AUTHOR]

Infantile botulism is a potentially life-threatening neuromuscular disorder. It presents with descending paralysis that can involve the diaphragm and cause respiratory failure. Neurally adjusted ventilatory assist (NAVA) provides synchronized bilevel positive pressure by using electrical diaphragmatic (Edi) signals. Diaphragmatic paresis is thought to be a contraindication for using NAVA. However, the use of a NAVA catheter allows continuous assessment of diaphragm activity in infantile botulism. We discuss a case of infantile botulism in an infant from central Pennsylvania who presented with poor oral feeding, hypothermia, and lethargy and progressed to develop apnea and acute respiratory failure. The infant was intubated and mechanically ventilated. A diagnosis of infantile botulism was confirmed through the detection of botulinum toxin in the infant's stool, and the infant was treated with botulism immune globulin neutralizing antibodies. During his recovery phase, a NAVA catheter was placed, which allowed monitoring of Edi signals to gauge the return of diaphragm activity and to assist with the assessment of extubation readiness. We describe the trends in this infant's Edi signals following administration of globulin neutralizing antibodies and the successful transition to invasive, and subsequently, noninvasive NAVA. Our report demonstrates the clinical utility of monitoring diaphragmatic activity using a NAVA catheter and that NAVA provided adequate respiratory support to an infant during the recovery phase of infantile botulism. [ABSTRACT FROM AUTHOR]

Background: Intragastric 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. Methods: We 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. Results: Seven 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. Conclusion: Our 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Clostridial infections in cattle are a major veterinary concern in Brazil, significantly impacting the country's livestock industry. These infections are caused by various Clostridium species, which are anaerobic, spore-forming bacteria capable of producing powerful toxins. The main clostridial diseases affecting cattle in Brazil include botulism, tetanus, blackleg, malignant edema and enterotoxemia. Prevention and control measures of regular vaccination programs are crucial in preventing clostridial diseases. Ensuring proper hygiene, especially during surgical procedures, and minimizing injuries can help reduce the risk of infection. Surveillance and research are essential for understanding the epidemiology of these diseases and improving control strategies. Monitoring outbreaks and investigating new cases help in adapting vaccination protocols and management practices. The economic impact of clostridial infections causes significant economic losses in Brazil's cattle industry due to high mortality rates, decreased productivity, and the costs associated with vaccination and treatment. Effective prevention and control strategies are crucial to mitigate these losses and ensure the health and productivity of cattle herds. Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus is less common, but it is a serious disease that follows the contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is a disease that primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, and it can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causes sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability. [ABSTRACT FROM AUTHOR]

Botulism is a deadly neuroparalytic condition caused by the botulinum neurotoxin (BoNT) produced by Clostridium botulinum and related species. Toxin‐neutralizing antibodies are the most effective treatments for BoNT intoxication. We generated human monoclonal antibodies neutralizing type B botulinum neurotoxin (BoNT/B), designated M2 and M4. The combination of these antibodies exhibited a strong neutralizing effect against BoNT/B toxicity. In this study, we analyzed the mechanisms of action of these antibodies in vitro. M4 binds to the C‐terminus of the heavy chain (the receptor‐binding domain) and inhibits BoNT/B binding to neuronal PC12 cells. Although M2 recognized the light (L) chain (the metalloprotease domain), it did not inhibit substrate (VAMP2) cleavage in the cleavage assay. M2 increased the surface localization of BoNT/B in PC12 cells at a later time point, suggesting that M2 inhibits the translocation of the L chain from synaptic vesicles to the cytosol. These results indicate that M2 and M4 inhibit the different processes of BoNT/B individually and that multistep inhibition is important for the synergistic effect of the combination of monoclonal antibodies. Our findings may facilitate the development of effective therapeutic antibodies against BoNTs. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E--key contributors to the vast majority of human botulism--we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broadspectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies. [ABSTRACT FROM AUTHOR]

Purpose: This case study examined long-term cognitive deficits after botulism. Only a very limited number of studies on post-acute cognitive impairment after botulism exist, and data are incomplete. Method: A semi-structured interview on long-term cognitive consequences of botulism was conducted for six family members, who contracted the infection after ingestion of lumpfish-roe 2.5 years ago. Two of the family members underwent neuropsychological assessment of attention, memory, and executive functioning as well. Finding: Results of the semi-structured interviews showed individual subjective cognitive deficits across processing speed, attention, concentration, shortand long-term memory, and executive functioning. Test results showed mild cognitive impairment in attention and mild--moderate deficits in executive functioning. Conclusion: These results support previous findings that patients of various infectious diseases may suffer unspecific long-term neurocognitive deficits. Assessment and initiation of relevant post-acute treatment and rehabilitation might be central to prognosis, functional ability, and psychological well-being. [ABSTRACT FROM AUTHOR]

BACKGROUND Botulinum neurotoxins produced by Clostridium botulinum consist of a complex of a core neurotoxin protein and one or more nontoxin accessory proteins. The accessory proteins are generally thought to protect the neurotoxin from the gastric environment in botulism poisoning, dissociating away upon absorption. Other than their questionable immunogenicity, they are rarely mentioned in botulinum toxin therapy. OBJECTIVE To review evidence that accessory proteins potentially play a role in neurotoxin activity. RESULTS Evidence suggests that the accessory proteins do not dissociate from the neurotoxin complex and enhance neurotoxin activity. Complexed type A botulinum toxin has dramatically higher endopeptidase activity than noncomplexed neurotoxin. A primary accessory protein, hemagglutinin-33, exhibits this same effect on both type A and type E core neurotoxin proteins, the latter not natively having this accessory protein. A clinical study using an objective computer assessment assay has shown a correlation between type A complex size and glabellar strain reduction, which reflects increasing clinical efficacy. Finally, a systematic review found no correlation between type A complex size and neutralizing antibody formation. CONCLUSION Accessory proteins may play a role in the efficacy of botulinum toxin and could remain complexed to the neurotoxin for longer than previously reported. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism. The present study aimed to establish a new scoring system to predict mechanical ventilation (MV) for botulism patients. METHODS: A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022. Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system. The area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: A total of 153 patients with botulism (66 males and 87 females, with an average age of 43 years) were included. Of these, 49 patients (32.0%) required MV, including 21 (13.7%) with invasive ventilation and 28 (18.3%) with non-invasive ventilation. Multivariate analysis revealed that botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement were independent risk factors for MV. These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system. Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization ([botulinum toxin type A: 1], [pneumonia: 2], [incubation period =1 day: 2], [hypoxia <90%: 2], [severity of muscle involvement: grade II, 3; grade III, 7; grade IV, 11]). The scoring system achieved an area under the ROC curve of 0.82 (95% CI 0.75-0.89, P<0.001). At the optimal threshold of 9, the scoring system achieved a sensitivity of 83.7% and a specificity of 70.2%. CONCLUSION: Our study identified botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement as independent risk factors for MV in botulism patients. A score =9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients. This scoring system needs to be validated externally before it can be applied in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Botulism has not been previously reported in the Kingdom of Saudi Arabia. This rare and sometimes fatal foodborne illness is caused by neurotoxins and primarily results from consuming home-canned fruits, vegetables, dairy, and seafood products & it can lead to paralysis. Objective: The purpose of this study was to evaluate the clinical features of patients who developed botulism in Riyadh in 2024 after consuming mayonnaise from a well-known local chain of restaurants in Riyadh, Saudi Arabia. Methods: We conducted a retrospective analysis of medical records and interviewed patients or their attendants for all hospitalized cases of foodborne botulism at Riyadh First Health Cluster. For each patient, a standard case report form was completed, containing information on demographics, clinical aspects, botulinum test results, and type of exposure. Descriptive statistics were applied to assess the data. During the outbreak, nineteen patients with foodborne diseases were admitted to Riyadh First Health Cluster Hospitals. Following thorough physical examinations, botulism was suspected in each case. Results: Eight of the 19 suspected foodborne illness patients fully satisfied the botulism case definition requirements set forth by the Saudi Arabian Public Health Authority (Weqaya). Among these eight patients, 2 (25%) were male and 6 (75%) were female, with a mean age of 23.25 ± 9.29 years (range: 12–38 years). The incubation period for our patients was 36.25 ± 26.26 h. Notable symptoms included dysphagia in all eight patients (100%), dysarthria, generalized weakness, nausea and vomiting in seven patients (88%), diplopia in four patients (50%), and stomach discomfort in three patients (38%). Of the eight cases, six required intubation, one mimicked brain death, and two were stable. The presence of Clostridium botulinum spores as the cause of the outbreak was confirmed by detecting botulinum spores in contaminated food. Conclusion: Diplopia and dysarthria were the most common early sign of botulism. Early manifestations may include respiratory symptoms without any musculoskeletal symptoms. or nausea, vomiting and disorientation. [ABSTRACT FROM AUTHOR]

Botulism is a rare cause of bulbar and oculomotor syndromes. A late diagnosis and, therefore, late initiation of specific therapy may lead to multiple life-threatening complications. Epidemiological history and clinical findings are key to the correct diagnosis, but if these data are not available due to atypical clinical findings, botulism identification is challenging. In our clinical case, a 31-year-old man was admitted to the hospital with double vision, impaired eye movements, and difficulty swallowing rapidly developing for 2 days. Ocular motility dysfunction included disturbed conjugate eye movements. In young patients, this is most often caused by demyelinating disease with medial (posterior) longitudinal fasciculus damage and symmetrical bilateral ptosis. The patient denied eating foods that could cause botulism and did not have any gastrointestinal symptoms. Differential diagnoses included demyelinating disease onset and Miller–Fisher syndrome. The next morning, completely identical clinical signs appeared in the patient’s mother who had eaten canned mushrooms, so botulism was suspected. Over the next few hours, despite the administration of anti-botulinum serum, acute respiratory failure developed, and the patient was placed on a ventilator for 28 days. The patient and his mother were discharged in a satisfactory condition, and their symptoms completely resolved within a few months. The diagnosis of botulism was confirmed by toxicological examination.

INTRODUCTION. The outbreak of foodborne botulism that occurred in Russia in June 2024 once again demonstrated the danger of this rather rare but severe infectious disease caused by ingesting botulinum neurotoxin. The only aetiological treatment for botulism is currently the administration of antitoxins against various serotypes of botulinum toxin. However, antitoxins do not provide rapid regression of neurological symptoms, which may raise doubts about the effectiveness of the selected treatment option. It is impossible to assess the potential of specific treatment without understanding the mechanisms of action of botulinum toxin and antitoxin.AIM. This study aimed to systemise information on the mechanism underlying the damaging effect of botulinum neurotoxin, aetiological antitoxin treatment, and the patient recovery process.DISCUSSION. The mechanism underlying the damaging effect of botulinum neurotoxin consists in the destruction of SNARE proteins in presynaptic cholinergic nerve terminals, which disrupts the release of acetylcholine into the synaptic cleft and the transmission of excitation between neurons. The lack of acetylcholine at the neuromuscular junction results in a distinctive form of persistent flaccid paralysis. The specific mechanism of action of botulinum toxin determines the treatment strategy, which includes a set of life-sustaining measures and the earliest possible antiserum administration. If used within 48 hours from the onset of symptoms, botulinum antitoxin binds botulinum toxin circulating in the blood, which stops the progression of paralysis and prevents further disorders in patients. However, botulinum antitoxin cannot neutralise the effect of the toxin that has already bound to nerve receptors, so clinical symptoms may worsen within 12 hours after antiserum administration. Restoration of normal neuronal transmission occurs through the formation of new axonal sprouts and can take a long time.CONCLUSIONS. Antitoxin administration is effective and irreplaceable in the aetiological treatment of botulism. Nevertheless, the duration of recovery depends on the speed of reinnervation and restoration of transmission at the neuromuscular junction.

Botulism is an acute infectious disease caused by a neutrotoxin produced by the bacterium Clostridium botulinum and characterized by severe bulbar lesions. Botulism is characterized by the complexity of diagnosis and in adverse cases can lead to death. At the moment, in the complex therapy of botulism, the introduction of a mixture of antitoxic serums is mandatory. In addition to specific treatment, pathogenetic therapy is performed for all patients. Specific prophylaxis is carried out with polyanatoxin to a narrow group of people in contact with Clostridium botulinum or their toxins. However, neutralizing anti-botulinum antibodies may be detected in the blood serum of a number of individuals, which have a protective effect when encountering an infection. This article presents a clinical case of severe botulism in an adult patient with simultaneous absence of symptoms of the disease in family members.Botulinum toxin preparations have long been used in aesthetic medicine. It is worth noting that the botulinum toxin molecule has a high molecular weight and can cause an immune response with repeated injections, especially in areas rich in lymph nodes. Forming specific antibodies belong to the IgG class and may have neutralizing properties. In the above clinical case, the patient’s wife, during repeated injections of botulinum toxin, most likely, the formation of neutralizing antibodies occurred, which, in turn, protected the woman from the disease.

In recent years, the incidence of cosmetic injection-induced botulism has remarkably increased due to the frequent usage of botulinum neurotoxin type A (BoNT/A). To mimic and investigate this new clinical type of botulism, we established a novel animal model and evaluated the therapeutic potential of a new drug. Firstly, we injected BoNT/A into the gastrocnemius of rats to induce partial paralysis of the remaining limbs. Then, the intoxicated rats were treated with 3,4-diaminopyridine (3,4-DAP) at different stages of the disease and the forelimbs grasping strength (FGS) was evaluated. We showed that, at the sublethal dose, the FGS began to decrease at 6.00 ​± ​1.86 ​h after injection in rats, from 2.28 ​± ​0.19 ​N to 1.51 ​± ​0.18 ​N, while the FGS declined appeared earlier (4.29 ​± ​0.42 ​h) at the lethal dose, from 2.30 ​± ​0.20 ​N to 1.20 ​± ​0.16 ​N. Treatment with 3,4-DAP respectively at the time of the symptoms onset or 7 days after injection both can temporarily reverse the symptoms of muscle paralysis, indicating that 3,4-DAP may be an effective approach to relieve botulism. Overall, this study provides an available rat model and a promising therapeutic strategy for cosmetic injection-induced botulism.

Botulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach. Therefore, it is important to obtain effective neutralizing nanoantibodies. Hence, the present study aimed to construct a phage antibody library by immunizing a camel and screening specific clones that bind to the L-HN domain of BoNT/F and constructing chimeric heavy-chain antibodies by fusing them with a human Fc fragment. The antibodies' affinity and in vivo neutralizing activities were evaluated. The results showed that 2 µg of F20 antibody could completely neutralize 20 × the median lethal dose (LD50) of BoNT/F in vitro. Injection of 5 mg/kg F20 at 1 h, 2 h, 3 h, and 4 h into mice after BoNT/F challenge resulted in complete survival in vivo. Overall, the antibody might be a candidate for the development of new drugs to treat botulism. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Botulism has not been previously reported in the Kingdom of Saudi Arabia. This rare and sometimes fatal foodborne illness is caused by neurotoxins and primarily results from consuming home-canned fruits, vegetables, dairy, and seafood products & it can lead to paralysis. Objective The purpose of this study was to evaluate the clinical features of patients who developed botulism in Riyadh in 2024 after consuming mayonnaise from a well-known local chain of restaurants in Riyadh, Saudi Arabia. Methods We conducted a retrospective analysis of medical records and interviewed patients or their attendants for all hospitalized cases of foodborne botulism at Riyadh First Health Cluster. For each patient, a standard case report form was completed, containing information on demographics, clinical aspects, botulinum test results, and type of exposure. Descriptive statistics were applied to assess the data. During the outbreak, nineteen patients with foodborne diseases were admitted to Riyadh First Health Cluster Hospitals. Following thorough physical examinations, botulism was suspected in each case. Results Eight of the 19 suspected foodborne illness patients fully satisfied the botulism case definition requirements set forth by the Saudi Arabian Public Health Authority (Weqaya). Among these eight patients, 2 (25%) were male and 6 (75%) were female, with a mean age of 23.25 ± 9.29 years (range: 12–38 years). The incubation period for our patients was 36.25 ± 26.26 h. Notable symptoms included dysphagia in all eight patients (100%), dysarthria, generalized weakness, nausea and vomiting in seven patients (88%), diplopia in four patients (50%), and stomach discomfort in three patients (38%). Of the eight cases, six required intubation, one mimicked brain death, and two were stable. The presence of Clostridium botulinum spores as the cause of the outbreak was confirmed by detecting botulinum spores in contaminated food. Conclusion Diplopia and dysarthria were the most common early sign of botulism. Early manifestations may include respiratory symptoms without any musculoskeletal symptoms. or nausea, vomiting and disorientation.

Simple Summary: In all continents, except in Antarctica, avian botulism outbreaks occur in wild waterbirds with different recurrences and a high severity. This feared disease is due to the ingestion of botulinum neurotoxins (BoNT) mainly produced by Clostridium botulinum, also able to produce persistent spores representing an efficient form of environmental resistance while waiting for suitable conditions enabling bacterial vegetative growth. In addition, concomitant ecological and environmental changes (e.g., the presence of decaying organic material of plant and animal origins) represent a suitable substrate for the replication of Clostridium spp. strains producing BoNT in conditions of high temperatures and the absence of oxygen. This study describes the occurrence, evolution, and management of a severe outbreak of botulism that occurred in a protected wetland area of northeastern Italy, where over 2000 waterbirds (mostly carcasses, and only to a lesser extent sick birds) were recovered in 2019. We also describe the activities underlying the avian botulism monitoring and management performed in this area in 2020, 2021, and 2022. According to an ecological approach, anthropogenic changes that may trigger the occurrence of avian botulism in wetland habitats should be carefully assessed, and habitat management actions should be adaptively planned to protect the biodiversity of these vulnerable ecosystems, which are increasingly affected by ongoing global change. Avian botulism is a paralytic disease due to the ingestion of botulinum neurotoxins (BoNT) produced by anaerobic, sporigenic bacteria (notably, Clostridium botulinum). Wild waterbirds worldwide are affected with variable recurrence and severity, and organic material decaying in wetland habitats may constitute a suitable substrate for the replication of clostridia strains producing BoNT in conditions of high temperatures and the absence of oxygen. Here, we describe a large outbreak of avian botulism that occurred in the Valle Mandriole protected area of northeastern Italy (VM). After the recovery in late summer of a few duck carcasses that molecularly tested positive for BoNT-producing clostridia, in October 2019, the avian botulism escalation led to a total of 2367 birds being recovered (2158 carcasses and 209 sick birds). Among these, 2365/2367 were waterbirds, with ducks accounting for 91.8% of the total (2173/2367) and green-winged teals representing 93.5% of the ducks. After the quick collection of dead and sick birds (from 4 to 11 October 2019) and the flooding of the VM wetland (from 5 to 12 October 2019), the 2019 botulism emergency apparently ended. Following two water inputs in May and July 2020, only one pooled sample obtained from 16 bird carcasses found that year in VM tested positive for clostridia type C by real-time PCR, whereas, after to the implementation of measures deterring the bird's presence, new avian botulism cases—due to clostridia type C and C/D, according to molecular and animal-model tests of confirmation—led to the collection of 176 waterbirds (82 carcasses and 94 sick ducks) and 16 waterbirds (9 carcasses and 7 sick ducks) in the summers 2021 and 2022, respectively. In conclusion, the prevention, management, and control of the disease rely on habitat management, the quick and careful collection/removal of animal carcasses, and the regular monitoring and surveillance of live and dead birds. [ABSTRACT FROM AUTHOR]

Recombinant mutant holotoxin BoNTs (rBoNTs) are being evaluated as possible vaccines against botulism. Previously, several rBoNTs containing 2–3 amino acid mutations in the light chain (LC) showed significant decreases in toxicity (2.5-million-fold–12.5-million-fold) versus wild-type BoNT/A1, leading to their current exclusion from the Federal Select Agent list. In this study, we added four additional mutations in the receptor-binding domain, translocation domain, and enzymatic cleft to further decrease toxicity, creating 7M rBoNT/A1. Due to poor expression in E. coli, 7M rBoNT/A1 was produced in an endogenous C. botulinum expression system. This protein had higher residual toxicity (LD50: 280 ng/mouse) than previously reported for the catalytically inactive rBoNT/A1 containing only three of the mutations (>10 µg/mouse). To investigate this discrepancy, several additional rBoNT/A1 constructs containing individual sets of amino acid substitutions from 7M rBoNT/A1 and related mutations were also endogenously produced. Similarly to endogenously produced 7M rBoNT/A1, all of the endogenously produced mutants had ~100–1000-fold greater toxicity than what was reported for their original heterologous host counterparts. A combination of mutations in multiple functional domains resulted in a greater but not multiplicative reduction in toxicity. This report demonstrates the impact of production systems on residual toxicity of genetically inactivated rBoNTs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Botulism is a serious condition that carries with it a high rate of morbidity and mortality. This review highlights the pearls and pitfalls of botulism, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. 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. An understanding of botulism and its many potential mimics can assist emergency clinicians in diagnosing and managing this deadly disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Botulinum neurotoxins (BoNTs) cause botulism and are the most potent natural toxins known. Immunotherapy with neutralizing monoclonal antibodies (MAbs) is considered to be the most effective immediate response to BoNT exposure. Hybridoma technology remains the preferred method for producing MAbs with naturally paired immunoglobulin genes and with preserved innate functions of immune cells. The affinity-matured human antibody repertoire may be ideal as a source for antibody therapeutics against BoNTs. In an effort to develop novel BoNT type A (BoNT/A) immunotherapeutics, sorted by flow cytometry plasmablasts and activated memory B cells from a donor repeatedly injected with BoNT/A for aesthetic botulinum therapy could be used due to obtain hybridomas producing native antibodies. Methods: Plasmablasts and activated memory B-cells were isolated from whole blood collected 7 days after BoNT/A injection and sorted by flow cytometry. The sorted cells were then electrofused with the K6H6/B5 cell line, resulting in a producer of native human monoclonal antibodies (huMAbs). The 3 antibodies obtained were then purified by affinity chromatography, analyzed for binding by Western blot assay and neutralization by FRET assay. Results: We have succeeded in creating 3 hybridomas that secrete huMAbs specific to native BoNT/A and the proteolytic domain (LC) of BoNT/A. The 1B9 antibody also directly inhibited BoNT/A catalytic activity in vitro. Conclusion: The use activated plasmablasts and memory B-cells isolated at the peak of the immune response (at day 7 of immunogenesis) that have not yet completed the terminal stage of differentiation but have undergone somatic hypermutation for hybridization allows us to obtain specific huMAbs even when the immune response of the donor is weak (with low levels of specific antibodies and specific B-cells in blood). A BoNT/A LC-specific antibody is capable of effectively inhibiting BoNT/A by mechanisms not previously associated with antibodies that neutralize BoNT. Antibodies specific to BoNT LC can be valuable components of a mixture of antibodies against BoNT exposure. [ABSTRACT FROM AUTHOR]

Botulism is one of the most serious food intoxications, manifesting as prolonged paralytic conditions. This disease is usually the result of the consumption of poor quality canned or smoked foods, so the inhabitants of many countries of the world are exposed to the risk of this kind of poisoning every year. In view of the severity of poisonings caused by botulinum neurotoxins, monoclonal antibodies (mAbs) show great promise because of their targeting action, lack of allergic reactions and serum sickness. The use of a cocktail of mAbs increases the "functional specificity" of their mixture, allowing them to bind to the active domains of different toxin chains and block their action. In this work, we obtained 14 murine mAbs to the catalytic and receptor-binding domain of botulinum toxin type A. The Sp2/0-Ag14 murine myeloma cell line and splenocytes from immunized mice of the BALB/c line were used as fusion partners. We have shown that the selected cocktail of three antibodies neutralizes native toxin more effectively than antibodies separately—complete neutralization is achieved at a toxin dose of 3LD50 and partial neutralization at 5LD50. We presume that this cocktail may be promising as a prototype for the creation of a therapeutic drug capable of neutralizing the toxin in the blood of patients. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins are some of the most potent natural toxins known; they cause flaccid paralysis by inhibiting synaptic vesicle release. Some serotypes, notably serotype A and B, can cause persistent paralysis lasting for several months. Because of their potency and persistence, botulinum neurotoxins are now used to manage several clinical conditions, and there is interest in expanding their clinical applications using engineered toxins with novel substrate specificities. It will also be beneficial to engineer toxins with tunable persistence. We have investigated the potential use of small-molecule proteolysis-targeting chimeras (PROTACs) to vary the persistence of modified recombinant botulinum neurotoxins. We also describe a complementary approach that has potential relevance for botulism treatment. This second approach uses a camelid heavy chain antibody directed against botulinum neurotoxin that is modified to bind the PROTAC. These strategies provide proof of principle for the use of two different approaches to fine tune the persistence of botulinum neurotoxins by selectively targeting their catalytic light chains for proteasomal degradation. [ABSTRACT FROM AUTHOR]

Background: Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulisminfected and healthy infants as well as the dynamic changes over time through multi-omics analysis. Methods: We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series. Results: We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32. Conclusion: Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants. [ABSTRACT FROM AUTHOR]

ABSTRACT: Botulism is a neuroparalytic disease caused by ingesting neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum. It is a significant cause of cattle mortality in Brazil. BoNTs block the release of acetylcholine at the neuromuscular synapses and cause muscle flaccidity. The diagnosis of botulism is challenging due to two main factors: the absence of macro and microscopic lesions and the difficulties inherent in laboratory tests considered the gold standard for botulism. Due to these difficulties, reviews of botulism diagnoses in Mato Grosso do Sul and extensively in the Center-West of Brazil became discrepant according to the diagnostic methodology used, making it difficult to correctly assess the disease’s prevalence, epidemiology, and clinical picture. This study aimed to review the diagnoses of botulism in cattle reported in Brazil, comparing the criteria used in each case. We studied the cause, the pathogenesis, clinical signs, and all the diagnosis methods applied to botulism. Based on the subject reviewed, we propose a diagnostic protocol based on standards adequate to the Brazilian circumstances. We also reviewed the critical diseases of cattle diseases to be included in the differential diagnosis of botulism.

Introduction Botulinum toxin is a neurotoxin produced by the gram-positive bacteria Clostridium botulinum. Botulinum toxin has found great interest in the field of aesthetic medicine, but it has many other applications in other areas of medicine. Aim of the study The aim of this comprehensive review is to provide an overview of the usage of botulinum toxin in medicine, with a focus on specific areas of medicine. Attention will be paid to the safety of the use of this substance, taking into account its molecular structure and mechanism of action. Materials and methods An analysis of the scientific articles available in the Pubmed, Google Scholar and web of science databases was performed. Recent publications which most appropriately encompassed the issues under discussion have been selected for the purpose of this study. The process of search was carried out with the following keywords: neurotoxin, botulinum toxins, botulism, muscle paralysis. Summary Despite numerous studies, there is ample room for further research into the safety of using botulinum toxin in patients as well as new therapies with this substance. Botulinum toxin is a neurotoxin that is widely used in medicine, but has many side effects.

PurposeThis case study examined long-term cognitive deficits after botulism. Only a very limited number of studies on post-acute cognitive impairment after botulism exist, and data are incomplete.MethodA semi-structured interview on long-term cognitive consequences of botulism was conducted for six family members, who contracted the infection after ingestion of lumpfish-roe 2.5 years ago. Two of the family members underwent neuropsychological assessment of attention, memory, and executive functioning as well.FindingResults of the semi-structured interviews showed individual subjective cognitive deficits across processing speed, attention, concentration, short-and long-term memory, and executive functioning. Test results showed mild cognitive impairment in attention and mild–moderate deficits in executive functioning.ConclusionThese results support previous findings that patients of various infectious diseases may suffer unspecific long-term neurocognitive deficits. Assessment and initiation of relevant post-acute treatment and rehabilitation might be central to prognosis, functional ability, and psychological well-being.

In February 2023, a report of morbidity and mortality in waterbirds triggered a collaborative regional wildlife disease outbreak investigation and response, led by Parks Victoria. Triage, rehabilitation and diagnosis of sick and dead birds were undertaken by Zoos Victoria (ZV), Agriculture Victoria, Vets for Compassion, Wildlife Victoria and Melbourne Veterinary School (MVS). The field response focused on collection of sick and dead birds for wildlife welfare, for diagnosis, and to reduce environmental contamination. Botulism was suspected, based on clinical signs and lack of significant gross pathology, and this diagnosis was confirmed by PCR testing. Low pathogenicity avian influenza (LPAI) viruses non H5 or H7 were detected in two birds and ruled out in all in others tested. These incidental, non‐clinical LPAI detections are considered part of the natural wild bird virus community in Australia. A number of elements contributed to the collaborative effort. Regional individuals had the necessary connections for reporting, collecting and transporting birds. There was rapid determination by the Victorian Department of Energy, Environment and Climate Action (DEECA) that Parks Victoria, as the land managers, should lead the response. Zoos Victoria provided capacity and expertise in wildlife triage and rehabilitation, and Agriculture Victoria, ZV and MVS were responsible for veterinary management of the response and diagnosis. Field investigation and response were conducted by Parks Victoria, Agriculture Victoria, MVS and veterinary teams from Vets for Compassion and Wildlife Victoria. Wildlife Health Australia (WHA) provided guidance and information, approved National Significant Disease Investigation Program funding and captured the event in the national wildlife health information database. Communication and media were important for community understanding of the event. [ABSTRACT FROM AUTHOR]

ABSTRACTBotulism 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.

Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT/G at a total mAb dose of 6.25 μg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product.

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. [ABSTRACT FROM AUTHOR]

Botulism is a rare, potentially fatal illness caused by botulinum toxins produced by Clostridium bacteria. There are no coordinated worldwide reporting mechanisms for botulism cases and therefore few reliable case frequency estimates. This study aimed to establish an international benchmark for case frequency to determine estimated global rates of underreporting of botulism cases. To this end, a comprehensive, multilingual search of major global and national databases, including gray data and government sources, was performed. Data from case series were pooled, standardized against United Nations midyear population estimates, and analyzed using Kolmogorov-Smirnov tests to identify normally distributed data series. National incidence rates of normally distributed series were compared with that of the United States, which was considered the gold standard due to its extensive data reported for 2004-2018. A total of 6,932 botulism cases from 59 nations were identified in the literature, with a global case fatality rate of 1.37%. The national mean incidence rate ranged from 0.00 to 8.04 cases per million people, with an international mean incidence rate of 0.62 cases per million people. At the continent level, incidence rates tended toward normal distributions, although few countries outside of North America and Europe exhibited normal distributions. Based on comparisons with the US standard, an estimated 88.71% of botulism cases worldwide were unreported in 2016. Better awareness of botulism among healthcare professionals, coordinated global reporting mechanisms, and research on additional contributing factors to underreporting would enable better understanding of global case frequency, thereby potentially reducing the global incidence of botulism and improving outcomes. [ABSTRACT FROM AUTHOR]

Botulism is a priority disease worldwide because it has a very severe course of evolution that can lead to death. This paper aims to describe the main epidemiological characteristics of botulism cases confirmed in Romania over 14 years (2007–2020). We performed a retrospective study using the publicly available national surveillance data and reported to the National Institute of Public Health. A total of 325 cases of foodborne botulism were reported in Romania, with no infant or wound botulism. Most of the cases (125, 38.5%) were reported among young adults (25–44 years old), over half (205, 63%) of them living in rural areas. The incriminated food item was identified in 161 cases; in most cases (145, 90%) the food item was prepared in the household. The main food category was represented by meat and meat-based products (94, 68.6%). In almost all cases the identified type was BoNT/B (230/231, 99.5%). Fifteen deaths were recorded, and the case fatality rate was 4.6%. Botulism cases were reported annually in Romania. Surveillance data are essential for implementing control measures and adapting educational campaigns according to existing needs. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Infantile spondylodiscitis is a rare condition with a varied clinical presentation. Microbial infection may not always be identified, but early diagnosis and management are required to prevent long-term and irreversible complications, including spinal deformities and vertebral instability. Case Report: This report is of a 21-month-old girl with a 3-week history of difficulty in walking and constipation due to L1-L2 spondylodiscitis following a gluteal skin burn. The family had sought medical advice multiple times, but results of all investigations were unremarkable. Her initial spine X-ray was negative but her spine magnetic resonance imaging (MRI) showed a picture suggestive of spondylodiscitis, which then responded to empiric treatment with broad-spectrum antibiotics. The patient showed complete resolution of clinical symptoms and her bowel habits came back to normal after 6 months of complete antibiotics treatment. Her repeat spine MRI showed a significant improvement of her spondylodiscitis. Conclusions: This report has highlighted the importance of rapid diagnosis and management of infantile spondylodiscitis and the challenging approach to treatment when no infectious organism can be identified, as well as the early initiation of antibiotics therapy when appropriate in pediatric patients to avoid serious neurological complications associated with spondylodiscitis. Thus, it is essential to assess children with refusal to walk, gait problems, or back discomfort, especially when they are associated with high inflammatory markers. [ABSTRACT FROM AUTHOR]