Foodborne botulism presenting as small bowel obstruction: a case report.

BACKGROUND: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment. CASE PRESENTATION: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution. CONCLUSIONS: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.

Emergency response to a cluster of suspected food-borne botulism in Abuja, Nigeria: challenges with diagnosis and treatment in a resource-poor setting.

Food-borne botulism is a rare, acute and potentially fatal neurologic disorder that results from ingestion of food contaminated by botulinum toxin released from the anaerobic, spore-forming, gram-positive bacterium Clostridium botulinum. We reported an unusual cluster of botulism outbreak with high case fatality affecting a family following ingestion of home-made fish. A suspected outbreak of botulism affecting three patients in a family of six was reported to the Nigeria Centre for Disease Control. A rapid response team investigated by line-listing all the family members, interviewed extended family members, caregivers, clinicians, and nurses to collect socio-demographic and clinico epidemiological information using a semi-structured questionnaires. We collected blood from patients and food samples and locally made drink from the family home for laboratory testing. All family members ingested the same home-made food within the 48hrs before onset of symptoms in the index case. The clinical presentation of the three affected cases (AR=50.0%) was consistent with botulinum poisoning. Two of the affected cases died (CFR=66.7%) within 48hrs of admission, before antitoxin was made available. The third case had a milder presentation and survived, after administration of appropriate antitoxin. The remaining three children developed no symptoms. None of the samples cultured Clostridium botulinum. The blood samples were negative for mouse lethality test. Our report describes the challenges of diagnosis and management of rare emerging infectious disease outbreaks in resource-constrained settings.

Esophagogastric junction outflow obstruction: Where are we now in diagnosis and management?

Esophagogastric junction outflow obstruction (EGJOO) is a major motility disorder based on the Chicago Classification of esophageal motility disorders. This entity involves a heterogenous group of underlying etiologies. The diagnosis is reached by performing high-resolution manometry. This reveals evidence of obstruction at the esophagogastric junction, manifested by an elevated integrated relaxation pressure (IRP) above a cutoff value (IRP threshold varies by the manometric technology and catheter used), with preserved peristalsis. Further tests like endoscopy, timed barium esophagram, and cross-sectional imaging can help further elucidate the underlying etiology and rule out mechanical causes. Treatment is tailored to the underlying cause. Similar to achalasia, treatment targeting lower esophageal sphincter disruption like pneumatic dilation, peroral endoscopic myotomy, and botulinum injection are used in patients with functional EGJOO and persistent symptoms.

Efficacy of equine botulism antitoxin in botulism poisoning in a guinea pig model.

BACKGROUND: Botulism is a disease caused by neurogenic toxins that block acetylcholine release, resulting in potentially life threatening neuroparalysis. Seven distinct serotypes of botulinum neurotoxins (BoNTs) have been described and are found in nature world-wide. This, combined with ease of production, make BoNTs a significant bioweapon threat. An essential countermeasure to this threat is an antitoxin to remove circulating toxin. An antitoxin, tradename BAT (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)), has been developed and its efficacy evaluated against all seven serotypes in guinea pigs. METHODS AND FINDINGS: Studies were conducted to establish the lethal dose and clinical course of intoxication for all seven toxins, and post-exposure prophylactic efficacy of BAT product. Animals were monitored for signs of intoxication and mortality for 14 days. Guinea pig intramuscular LD50s (GPIMLD50) for all BoNTs ranged from 2.0 (serotype C) to 73.2 (serotype E) of mouse intraperitoneal LD50 units. A dose of 4x GPIMLD50 was identified as the appropriate toxin dose for use in subsequent efficacy and post-exposure prophylaxis studies. The main clinical signs observed included hind limb paralysis, weak limb, change in breathing rate/pattern, and forced abdominal respiration. Mean time to onset of clinical signs ranged from 12 hours (serotype E) to 39 hours (serotype G). Twelve hours post-intoxication was selected as the appropriate time point for intervention for all serotypes apart from E where 6 hours was selected because of the rapid onset and progression of clinical signs. Post-exposure treatment with BAT product resulted in a significantly (p<0.0001) higher survival at >0.008 scaled human dose for serotypes A, B, C, F and G, at >0.2x for serotype D and >0.04x for serotype E. CONCLUSIONS: These studies confirm the efficacy of BAT as a post-exposure prophylactic therapy against all seven known BoNT serotypes.

Clinical analysis of 86 botulism cases caused by cosmetic injection of botulinum toxin (BoNT).

This study was conducted to analyze the clinical characteristics of and treatment strategies for botulism among patients receiving cosmetic injection of botulinum toxin (BoNT).A total of 86 botulism patients caused by cosmetic injection of BoNT were enrolled in our study. All of the patients were diagnosed according to their history of cosmetic BoNT injection, clinical symptoms and signs, and other auxiliary examinations (including those on renal and liver functions, blood index detection, and chest X-ray). All of the patients received comprehensive treatments and botulinum antitoxin serum injection.The main symptoms of botulism patients included headache, dizziness, insomnia, fatigue, blurred vision, eye opening difficulty, slurred speech, dysphagia, bucking, constipation, and anxiety. These clinical symptoms occurred 0∼36 days after BoNT injection, especially from 2nd to 6th day after the operation. Furthermore, the usage dose of BoNT was negatively related to latent period. Finally, patients all discharged from our hospital 1∼20 days after treatments, and their symptoms relieved or disappeared.Botulism is a severe side effect for BoNT injection. Injecting botulinum antitoxin serum may be an effective approach to improve clinical outcomes of botulism cases.

Iatrogenic Botulism Outbreak in Egypt due to a Counterfeit Botulinum Toxin A Preparation - A Descriptive Series of Patient Features and Outcome.

Iatrogenic botulism resulting from the substantial increase in use of botulinum neurotoxin type A (BoNT-A) treatment is rarely reported. We aimed to describe a large iatrogenic botulism outbreak in Egypt in June-July 2017. Nine patients developed botulism after receiving intramuscular injections of BoNT-A (dose: 200-300 IU) to treat cerebral palsy (N = 7), spastic dystonia (N = 1) and hyperhidrosis (N = 1). Detailed findings were available in five of nine cases. Patients were admitted to the hospital 5-10 days after the BoNT-A injection. Complaints included muscle weakness in the upper and lower limbs (N = 5), dysphagia (N = 5), dizziness (N = 2), dyspnoea (N = 2), dysphonia (N = 2), dysarthria (N = 2), fatigue (N = 1), diplopia (N = 1) and blurred vision (N = 1). Physical examination showed bilateral ptosis (N = 5), diminished gag reflex (N = 2), ophthalmoparesis (N = 1), facial paresis (N = 1) and tongue weakness (N = 1). Diagnosis was based on the patients' history and presentation and did not require any confirmatory test. On hospital admission, patients received supportive care and trivalent botulism type A/B/E antitoxin (250-500 IU) was started. No patient required mechanical ventilation. Immediate reversal of the most severe features was observed while varying degrees of peripheral muscular weakness persisted. Full recovery required 6-12 weeks. Cases were promptly reported to the Egyptian health authorities, and epidemiological investigations revealed that the outbreak was related to a recently imported highly concentrated unlicensed BoNT-A preparation sold as Neuroxin® . Immediate withdrawal from the market was ordered. In conclusion, iatrogenic botulism outbreak due to counterfeit botulism toxin may result in life-threatening features. The early administration of botulism antitoxin in addition to supportive care is life-saving. Clinicians should remain mindful of the risk of systemic botulism with BoNT-A therapy.

Effective and rapid treatment of wound botulism, a case report.

BACKGROUND: The latest news shows several cases of contaminated heroin that is found in different parts all over Europe. This information can be helpful for the emergency doctors to find the correct diagnosis of wound botulism in patients who are intravenous drug users. CASE PRESENTATION: We describe a case of a 40-year-old man who presented to the emergency department in 2016. He suffered from mild dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the cerebrum and the liquor were without any pathological results. We found out that the patient is an intravenous drug user and the clinical examination showed an abscess in the left groin. So we treated him with the suspected diagnosis of wound botulism. In the emergency operation we split the abscess, made a radical debridement and complementary treated him with a high dose of penicillin g and two units of botulism antitoxin. The suspected diagnosis was confirmed a few days later by finding the Toxin B in the abscess and in the patient's serum. In the following days the neurological symptoms decreased and the wound healing was without any complications. The patient left the hospital after nine days; the antibiotic therapy with penicillin g was continued for several days. In a following examination, 14 days after the patient's discharge of the hospital, no further symptoms were found and the abscess was treated successfully without any problems. CONCLUSION: Because wound botulism is a very rare disease it can be challenging to the attending physician. This case shows a fast treatment with full recovery of the patient without any further disabilities, which can be used for the future.

mRNA mediates passive vaccination against infectious agents, toxins, and tumors.

The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies. Single injections of mRNA-lipid nanoparticle (LNP) were sufficient to establish rapid, strong, and long-lasting serum antibody titers in vivo, thereby enabling both prophylactic and therapeutic protection against lethal rabies infection or botulinum intoxication. Moreover, therapeutic mRNA-mediated antibody expression allowed mice to survive an otherwise lethal tumor challenge. In conclusion, the present study demonstrates the utility of formulated mRNA as a potent novel technology for passive immunization.

Recent developments with metalloprotease inhibitor class of drug candidates for botulinum neurotoxins.

Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are potential biological warfare and bioterrorism agents due to their high toxicity and ease of preparation. On the other hand BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and with that the chances of accidental overdose are increasing. And despite the potential damage they could cause to human health, there are no post-intoxication drugs available so far. But progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been determined, and these are enabling structure-based drug discovery possible. High throughput assays have also been designed to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments and the future challenges in drug discovery for Botulinum neurotoxins.

Dos casos de botulismo alimentario en pacientes mayores de 75 años / Two cases of food-borne botulism in patients over 75 years of age

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New targets in the search for preventive and therapeutic agents for botulism.

Botulism is a severe neuroparalytic disease resulting from exposure to one of the most poisonous toxins to humans. Because of this high potency and the use of toxins as biological weapons, botulism is a public health concern and each case represents an emergency. Current therapy involves respiratory supportive care and anti-toxins administration. As a preventive measure, vaccination against toxins represents an effective strategy but is undesirable due the rarity of botulism and the effectiveness of toxins in treating several neuromuscular disorders. This paper summarizes the current issues in botulism treatment and prevention, highlighting the challenge for future researches.

[Familial occurrence of botulism - a case report]. / Familiarni vyskyt botulismu - kazuistika.

Botulism, a life-threatening condition, is very rare in the Czech Republic. Since 1960, a total of 155 cases have been reported; between 2010 and 2012, not a single case was identified. This is a case report of familiar occurrence of botulism following consumption of home-made pork and liver pâté in three family members admitted to the Department of Infectious, Tropical and Parasitic Diseases, Na Bulovce Hospital in Prague in May 2013. The neurological symptoms were dominated by diplopia and dysarthria. After administration of an antitoxin, all patients recovered. Given the poor availability of the antitoxin, a decision was made following this small family epidemic to have an emergency reserve of life-saving anti-infective drugs for the Czech Republic in the Toxicological Information Center in Prague.