Search

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.

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., Competing Interests: The authors declare no conflict of interests., (Copyright: Oyeladun Okunromade et al.)

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., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

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., Competing Interests: A. Emanuel and T. Takla were employees of Emergent BioSolutions Canada Inc. at the time of the study. Doug Barker, Hongyu Qiu, and Shantha Kodihalli are current employees of Emergent BioSolutions Canada Inc., who developed and manufactured the BAT and placebo employed in these studies. Karen Gillum, Nancy Neimuth are employees of Battelle Biomedical Research Center and claim no conflict of interest. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. Emergent BioSolutions, Protected by Emergent BioSolutions, BAT, and any and all Emergent BioSolutions Inc. brand, product, service and feature names, logos and slogans are trademarks or registered trademarks of Emergent BioSolutions Inc. or its subsidiaries in the United States or other countries. All other brand, product, service and feature names or trademarks are the property of their respective owners.

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., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

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.

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.

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., (© 2017 CureVac AG. Published under the terms of the CC BY 4.0 license.)

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.

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.

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.

Recent studies have shown that infraorbital nerve constriction (IoNC)-induced mechanical allodynia has been attenuated by administration of highly purified 150-kDa Botulinum neurotoxin type A (BoNT/A). Here, we extend these studies to determine whether BoNT/A could attenuate IoNC-induced symptoms of thermal hyperalgesia. Instead of testing head withdrawal thresholds, a thermal operant assay was used to evaluate cortical processing of sensory input following IoNC. In this assay, a fasted rat's desire to obtain a food reward (sweetened condensed milk) is coupled to its ability to tolerate facial contact with a warm (45 °C) thermode. Bilateral IoNC decreased the ratio of thermode contact duration/event, which is an indicative of thermal hyperalgesia. BoNT/A injection intradermally in the area of infraorbital nerve (IoN) innervation 7 days after IoNC resulted in decreased number of facial contacts and increased the ratio of contact duration/event (measured at 14 days after IoNC). The BoNT/A (2-200 pg) effects were dose dependent and statistically significant at 100 and 200 pg (P < 0·05). Complete reversal of thermal hyperalgesia symptoms was obtained with a 200-pg dose, without affecting sham rat behaviour. Off-site (neck) injection of BoNT/A did not relieve thermal hyperalgesia, while co-injection of BoNT/A with a neutralising antibody in the area of IoN innervation prevented relief of thermal hyperalgesia. Neither IoNC nor BoNT/A injection affected operant assay parameters with a 24 °C thermode, indicating selectivity of thermal hyperalgesia measurements. These results strongly suggest that intradermal injection of BoNT/A in the area of IoN innervation alleviates IoNC-induced thermal hyperalgesia in an operant assay., (© 2011 Blackwell Publishing Ltd.)

Here we introduce a new virtual reality (VR) based simulation system for training the urological procedure of intra-detrusor botulinum toxin (Botox®) injections into the bladder. 6 cases with different bladder anatomy and 3 subtasks are included in the curriculum; this design is guided by several expert urologists according to clinical needs and experience. These virtual bladder models can be deformed by a cystoscope model or penetrated by a needle model. Data of location and dose per injection are collected during the training. After compared among various options, magnetic motion-tracking devices are chosen and integrated onto replicas of cystoscopic instruments as the VR interface for the specific operation. A web/database based learning management platform (LMP) is developed for online data access and validation studies of the training system.

Investigational heptavalent botulinum antitoxin (HBAT) is now the primary antitoxin for US noninfant botulism patients. HBAT consists of equine Fab/F(ab')2 IgG fragments, which are cleared from circulation faster than whole immunoglobulins. Rebound botulism after antitoxin administration is not previously documented but occurred in our patient 10 days after HBAT administration.

Infant botulism is the most common form of human botulism in Argentina and the United States. BabyBIG (botulism immune globulin intravenous [human]) is the antitoxin of choice for specific treatment of infant botulism in the United States. However, its high cost limits its use in many countries. We report here the effectiveness and safety of equine botulinum antitoxin (EqBA) as an alternative treatment. We conducted an analytical, observational, retrospective, and longitudinal study on cases of infant botulism registered in Mendoza, Argentina, from 1993 to 2007. We analyzed 92 medical records of laboratory-confirmed cases and evaluated the safety and efficacy of treatment with EqBA. Forty-nine laboratory-confirmed cases of infant botulism demanding admission in intensive care units and mechanical ventilation included 31 treated with EqBA within the 5 days after the onset of signs and 18 untreated with EqBA. EqBA-treated patients had a reduction in the mean length of hospital stay of 23.9 days (P = 0.0007). For infants treated with EqBA, the intensive care unit stay was shortened by 11.2 days (P = 0.0036), mechanical ventilation was reduced by 11.1 days (P = 0.0155), and tube feeding was reduced by 24.4 days (P = 0.0001). The incidence of sepsis in EqBA-treated patients was 47.3% lower (P = 0.0017) than in the untreated ones. Neither sequelae nor adverse effects attributable to EqBA were noticed, except for one infant who developed a transient erythematous rash. These results suggest that prompt treatment of infant botulism with EqBA is safe and effective and that EqBA could be considered an alternative specific treatment for infant botulism when BabyBIG is not available.

CDC announces the availability of a new heptavalent botulinum antitoxin (HBAT, Cangene Corporation) through a CDC-sponsored Food and Drug Administration (FDA) Investigational New Drug (IND) protocol. HBAT replaces a licensed bivalent botulinum antitoxin AB and an investigational monovalent botulinum antitoxin E (BAT-AB and BAT-E, Sanofi Pasteur) with expiration of these products on March 12, 2010. As of March 13, 2010, HBAT became the only botulinum antitoxin available in the United States for naturally occurring noninfant botulism.

A 56-year-old woman in Helena, Montana, USA, who showed clinical signs of paralysis, received antitoxins to botulinum toxins A, B, and E within 24 hours; nevertheless, symptoms progressed to complete quadriplegia. On day 8, she began moving spontaneously, even though blood tests later showed botulinum toxin type F remained.

Persistence of circulating toxin in patients with foodborne botulism is not well characterized. Recommendations for administration of botulinum antitoxin are ambiguous for patients with late-presenting disease, such as a Florida woman with toxin-positive serum 12 days after toxin ingestion. We reviewed Alaska records of foodborne outbreaks of botulism that occurred during 1959-2007 to examine the period after ingestion during which toxin was detected. Of 64 cases with toxin-positive serum, toxin was detected up to 11 days after ingestion. The findings from Alaska and Florida support administration of antitoxin up to 12 days after toxin ingestion but do not indicate when circulating toxin should no longer be present.

A 4.5 months old, previously healthy Danish girl was admitted to a paediatric department after six days of passive behaviour and weak suck. Over the next days she became increasingly weak, developed bilateral ptosis, the muscle stretch reflexes were lost, and mydriasis with slow pupillary responses was noted. Botulism was suspected and confirmed by testing of patient serum in a bioassay. The condition of the patient improved following administration of botulism antiserum. The clinical picture was suggestive of intestinal (infant) botulism. However, botulism acquired from consumption of food with preformed neurotoxin could not be excluded.

A patient presented with a small-bowel obstruction associated with signs and symptoms of botulism. Fecal cultures were positive for viable Clostridium botulinum. This case emphasizes the importance of a broad differential diagnosis and doing a complete examination to account for all signs and symptoms.

History and Admission Findings: 5 heroin addicts (aged 31-44 years; 1 female, 4 men) presented with a history of blurred vision and diplopia followed by dysarthria. 3 of the patients also developed respiratory failure requiring long-term ventilatory support. Physical examination revealed cranial nerve deficits and abscesses at injection sites in 3 of them., Diagnosis: In 4 patients wound botulism was diagnosed on the basis of symptoms, course of the illness and response to specific treatment. Clostridium botulinum was grown from wound swab in one patient., Treatment and Course: Two of the patients, having been injected with antitoxin immediately after admission, were discharged almost symptom-free after only a few days. Adjuvant antibiotics and, in 3 patients, surgical débridement of the abscesses were needed., Conclusions: Progressive cranial nerve pareses in addicts who inject drugs intravenously or intramuscularly should raise the suspicion of wound botulism and require hospitalization. While indirect demonstration of toxin supports the diagnosis, false-negative results are common.

Wound botulism results from colonization of a contaminated wound by Clostridium botulinum and the anaerobic in situ production of a potent neurotoxin. Between 1943, when wound botulism was first recognized, and 1990, 47 laboratory-confirmed cases, mostly trauma-associated, were reported in the United States. Since 1990, wound botulism associated with injection drug use emerged as the leading cause of wound botulism in the United States; 210 of 217 cases reported to the Centers for Disease Control and Prevention between 1990 and 2002 were associated with drug injection. Despite the worldwide distribution of Clostridium botulinum spores, wound botulism has been reported only twice outside the United States, Europe, and Australia. However, wound botulism may go undiagnosed and untreated in many countries. We report two cases, both with type A toxin, from the Ecuadorian rain forest. Prompt clinical recognition, supportive care, and administration of trivalent equine botulinum antitoxin were life-saving.

Purpose: The proper dose, preparation, and storage of the formulation of botulinum neurotoxin serotype A (botulinum toxin type A) that is available in the United States (Botox) are described., Summary: The recommended dose of botulinum toxin type A varies widely from 1.25 Units to 100 Units, depending on the site. Small initial doses are used for patients without previous treatment with botulinum toxin. Repeat injections often are required, and subsequent doses should be individualized based on response. Larger repeat doses often are used when the response to initial doses is insufficient. An antitoxin is available in the event of accidental poisoning. Botulinum toxin type A is reconstituted with preservative-free 0.9% sodium chloride. Therefore, it should be stored in a refrigerator and discarded if more than four hours elapse after reconstitution., Conclusion: The safe and effective use of botulinum toxin type A requires the proper dose, preparation, and storage by trained personnel only.

Background: Botulism caused by type F botulinum toxin accounts for less than 0.1% of all human botulism cases and is rarely reported in the literature., Case Report: A 45-year-old woman presented to an emergency department complaining of blurred vision, difficulty focusing, and dysphagia. The treating physician initially considered the possibility of paralytic shellfish poisoning due to a report of shellfish ingestion, which was later determined to be frozen shrimp and a can of tuna, but no gastroenteritis or paresthesias were present. During the emergency department observation, the patient developed respiratory distress with hypercapnea and required intubation and mechanical ventilation. Within hours, ptosis, mydriasis, and weakness in the arms and legs developed. Bivalent (A, B) botulinum antitoxin was administered approximately 24 h from the onset of initial symptoms, but over the next two days complete paralysis progressed to the upper and lower extremities. Shortly thereafter a stool toxin assay demonstrated the presence of type F botulinum toxin. The patient subsequently received an experimental heptavalent botulinum antitoxin on hospital day 7 but paralysis was already complete. Her three-week hospital course was complicated by nosocomial pneumonia and a urinary tract infection, but she gradually improved and was discharged to a rehabilitation facility. Anaerobic cultures and toxin assays have yet to elucidate the source of exposure., Conclusion: We report a rare case of type F botulism believed to be foodborne in etiology. Administration of bivalent botulinum antitoxin did not halt progression of paralysis.

Side effects to botulinum antitoxins, including anaphylaxis and serum sickness, are common. This is due to the immunogenicity of the antitoxin, which can be measured by the production of anti-immunoglobulin antibodies. An ideal botulinum antitoxin would elicit a minimal production of anti-immunoglobulin antibodies from a patient, aiding its safety. To investigate the immunogenicity of different immunoglobulin fragments, whole IgG, F(ab')2 and Fab botulinum antitoxins were administered to mice by either the intravenous or intramuscular route. The production of anti-immunoglobulin antibodies was measured over time after a single dose of antitoxin, and the anti-immunoglobulin antibodies isotyped. When administered by the intramuscular route, Fab showed significantly lower immunogenicity than IgG, while F(ab')2 had an immunogenicity that was intermediate between the two. When administered by the intravenous route there was no significant difference in immunogenicity between IgG and F(ab')2 antitoxins, although Fab antitoxin had a significantly lower immunogenicity than either IgG or F(ab')2. IgG antitoxin was significantly more immunogenic by the intramuscular route than by the intravenous route. Sheep IgG had a lower immunogenicity than goat IgG in mice. There was no significant difference in immunogenicity between the two dosing routes for either F(ab')2 or Fab antitoxin. The anti-antibodies were predominantly IgG1, suggesting a strong Th2 bias to the anti-antibody response. In all cases, Fab represents the least immunogenic form of antitoxin.

BOTULISM AND BIOWARFARE: Botulism is a severe neuro-paralysing infection due to a toxin produced by Clostridium botulinum. The use of the botulinum toxin for terrorist aims in the form of aerosols is a perfectly credible eventuality. The botulinum toxin is the most potent toxin known; it is easy to produce and can lead to massive destruction., Depending on the Contamination: The clinical forms of botulism depend on the mode of contamination. Botulism through inhalation can only be the result of a deliberate act using an aerosol. The clinical symptomatology is identical to that of the other forms., Prevention: In the case of a bio-terrorist attack with an aerosol of botulinum toxin, the subjects exposed should be vaccinated as a prophylactic measure with trivalent antitoxin vaccine (types A, B and E). This vaccine must be administered as rapidly as possible in symptomatic patients. A single case of botulism acquired by inhalation corresponds to an act of terrorism.

In the paper we presented results of clinical and epidemiological analysis of 32 patients with botulism hospitalized at the Department of Infectious Diseases, Medical University of Lublin in 1990-2000. In the studied group, the relationships between botulism incidence and sex and place of residence were not significant. The incubation period ranged from 7 hours to 5 days (average 36 hrs). The clinical manifestations of botulism were typical in all cases. In one female patient the course of disease was complicated. She developed right-sided bronchopneumonia and left-sided purulent parotitis. The type B botulinum toxin occurred more frequently than the other types and the cases without serological confirmation (Chi 2 = 6.125 p = 0.01). It was found in serum of 23 patients (in 2 cases together with the type A toxin). The type E toxin was found in serum of one patient. The presence of toxin in serum was not detected in 8 patients. In all patients trivalent (types A, B and E) equine antitoxin was administered. The dose ranged from 50 to 150 cm3. Symptomatic treatment was given in all cases. Nobody required mechanical ventilation. The duration of hospitalization ranged from 5 to 28 days (average 16.6 days). A few patients complained of long-lasting blurred vision or dry mouth.

In a series of 33 blepharospasm patients who had the side effect of ptosis following therapeutic botulinum toxin type A (Botox: Allergan, Inc., Irvine, CA, U.S.A.) injection, we administered 41 injections of human botulinum immune globulin (IG) following injections of the toxin to test the dosage and timing of IG injection and its effectiveness in limiting or avoiding ptosis. An IG dose of 3.2 x 10(-3) international units (IU) per unit of Botox was effective in blocking toxin effect when injected into the same tissue site within 4 hours. An IG dose of 1.6 x 10(-2) to 3.2 x 10(-2) into the levator of the eye having more frequent ptosis in 19 patients reduced the incidence of ptosis to 11%. The fellow (control) eye had a ptosis incidence of 37%. No orbital hemorrhage or other adverse effect occurred from the IG or its injection.

The emphasis of immunization programs and schedules has traditionally been directed to infants and children, since most of the vaccine-preventable diseases are seen predominantly in these age groups. Immunization procedures in adults are less well defined but still of importance. Diseases for which immunizations are given before disease exposure include tetanus, diphtheria, influenza, rubella, and mumps; travelers to foreign countries may need immunizations against typhoid, cholera, yellow fever, typhus, poliomyelitis, plague, and viral hepatitis; other vaccines are available before disease exposure in unusual epidemiologic situations. After exposure to disease but before onset of symptoms, immunizations are available for rabies, viral hepatitis, and measles. After the onset of clinical illness, passive immunization should be given for tetanus, diphtheria, and botulism. This paper summarizes current practices for active and passive immunization against these diseases in adults.

The reaction of passive skin anaphylaxis was used to investigate the accumulation and the dynamics of skin-sensitizing antibodies (SSA) in the sera of guinea pigs immunized with botulin anatoxin by means of different methods: the aerosol and the subcutaneous method. In the aerosol-immunized animals (unlike the subcutaneously immunized ones) SSA appeared in a negligible amount only after the fourth immunization and disappeared rapidly.

The use of trivalent equine antitoxin in treating foodborne botulism has not been adequately assessed. One hundred thirty-two cases of type A foodborne botulism reported to the Centers for Disease Control in the period from 1973 to 1980 are reviewed to evaluate the effect of antitoxin therapy and other factors on the outcomes of patients with botulism. The fatality rates were higher in patients over 60 years old and in those who were index patients (the first or only patient in an outbreak). The clinical course was longer in patients over 60 years old, patients whose incubation period was less than 36 hours, and index patients. Patients who had received trivalent equine antitoxin had a lower fatality rate and a shorter course than those who did not receive antitoxin, even after controlling for age and incubation period. Patients who received antitoxin in the first 24 hours after onset had a shorter course but about the same fatality rate as those who received antitoxin later. These results suggest that trivalent antitoxin has a beneficial effect on survival and shortens the course of patients with type A botulism.

During an 11-year period (1967 through 1977) CDC monitored reactions of hypersensitivity to botulinal antitoxin of equine origin. Of 268 persons given botulinal antitoxin, 24 (9.0 percent) had nonfatal acute (5.3 percent) or delayed (3.7 percent) hypersensitivity reactions to a skin test or therapeutic dose. The over-all rate of reaction did not differ with the age or sex of the recipient or with the type (AB or ABE) of antitoxin administered. Serum sickness occurred significantly more frequently in persons who received more than 40 ml of serum antitoxin (p < 0.02). The over-all reaction, rate was higher than that associated with other equine serum products and probably cannot be substantially reduced. This risk, however, would be substantially reduced if not eliminated by using botulinal immune globulin obtained from hyperimmunized human donors.

Serum levels of equine-botulism antitoxin to toxin types A, B, and E were measured in four type-A botulism patients who had received equine-botulism antitoxin. High circulating levels capable of neutralizing in excess of 1 X 10(8), 9 X 10(7), and 6 X 10(6) 50% mouse lethal doses of toxin of types A, B, and E, respectively, were detected. There was little depletion of type-A antitoxin even though two of the patients had circulating type-A toxin before treatment. The half-life for antitoxin persistence for one patient was calculated as being 6.5, 7.6, and 5.3 days for antitoxin types A, B, and E, respectively. Antitoxin levels were not proportionate to the amount (range, 2-4 vials) injected and did not appear to be affected by whether the route of administration was iv or im. Peak serum levels of antitoxin were 10-1,000 times higher than amounts needed to neutralize the toxin measured in the serum of these and other patients with botulism.