An outbreak of type A botulism associated with a commercial cheese sauce

BACKGROUND: Although botulism is rare, recognition of a possible case of this illness represents a public health emergency. To prevent more cases, prompt investigation must be done to determine whether illness is linked to commercial product or restaurant. Botulism can masquerade as other illnesses, and seemingly unlikely foods can harbor botulinum toxin. OBJECTIVE: To confirm the diagnosis and determine the cause and extent of an outbreak of botulism associated with food served at a delicatessen. DESIGN: Retrospective cohort study of patrons of the delicatessen; laboratory analysis of food, serum samples, and stool samples; and traceback of implicated food. SETTING: Community in Georgia. PARTICIPANTS: Patrons of the delicatessen. MAIN OUTCOME MEASURES: Botulinum toxin in food, serum, or stool and Clostridium botulinum in food and stools. RESULTS: 8 of 52 patrons (15%) met the case definition for botulism. In 4 of the 8 patrons, and illness other than botulism was initially diagnosed. Five of the 8 were hospitalized, and 1 died. Stool cultures from 4 patrons yielded type AC. botulinum, and two serum samples contained botulinum toxin. All ill persons ate food from the delicatessen on 1 October 1993. Of the 22 persons who ate at the delicatessen that day, all 8 ill persons but none of the 14 well persons ate a potato stuffed with meat and cheese sauce. An open can of cheese sauce contained type A botulinum toxin and yielded C botulinum on culture. Cheese sauce experimentally inoculated with C botulinum spores became toxic after 8 days at a temperature of 22 degrees C (room temperature). CONCLUSIONS: A commercial, canned cheese caused a botulism outbreak. This product readily becomes toxic when contaminated by C botulinum spores and left at room temperature. Mild botulism caused by unusual vehicles may be misdiagnosed. Botulism should be included in the differential diagnosis of persons with signs or symptoms of acute cranial nerve dysfunction.     

The Brugada-Brugada syndrome. A contribution to detection of risk patients with reference to sudden heart death without structural heart disease

Infant botulism is caused by intestinal colonization by Clostridium botulinum, C. barati or C. butyricum. Infant botulism has only rarely been reported outside the USA. A 3-month-old boy developed constipation, lethargy, feeding difficulties and descending, severe, symmetric weakness. He was breastfed but had also been fed honey. Supportive care led to complete recovery. The serum was positive for C. botulinum toxin type A-F (mouse toxin neutralization assay). A strain of C. botulinum producing toxin type A and E was identified in the stool. C. botulinum was identified in a jar of honey of the same brand as the honey fed to the patient.     

Proton MR spectroscopy in infants with cerebral energy deficiency due to hypoxia and metabolic disorders

Botulism is a paralyzing disease caused by the toxin of Clostridium botulinum. The toxin produces skeletal muscle paralysis by producing a presynaptic blockade to the release of acetylcholine. Recent studies have pinpointed the site of action of the several types of botulinum neurotoxin at the nerve terminal. Since the discovery of the toxin about 100 years ago, five clinical forms of botulism have been described: 1) classic or foodborne botulism; 2) wound botulism; 3) infant botulism; 4) hidden botulism; 5) inadvertent botulism. A clinical pattern of descending weakness is characteristic of all five forms. Almost all human cases of botulism are caused by one of three serotypes (A, B, or E). Classic and wound botulism were the only two forms known until the last quarter of this century. Wound botulism was rare until the past decade. Now there are increasing numbers of cases of wound botulism in injecting drug users. Infant botulism, first described in 1976, is now the most frequently reported form. In infant botulism spores of Clostridium botulinum are ingested and germinate in the intestinal tract. Hidden botulism, the adult variant of infant botulism, occurs in adult patients who usually have an abnormality of the intestinal tract that allows colonization by Clostridium botulinum. Inadvertent botulism is the most recent form to be described. It occurs in patients who have been treated with injections of botulinum toxin for dystonic and other movement disorders. Laboratory proof of botulism is established with the detection of toxin in the patient's serum, stool, or wound. The detection of Clostridium botulinum bacteria in the stool or wound should also be considered evidence of clinical botulism. Electrophysiologic studies can provide presumptive of botulism in patients with the clinical signs of botulism. Electrophysiologic testing can be especially helpful when bioassay studies are negative. The most consistent electrophysiologic abnormality is a small evoked muscle action potential in response to a single supramaximal nerve stimulus in a clinically affected muscle. Posttetanic facilitation can be found in some affected muscles. Single-fiber EMG studies typically reveal increased jitter and blocking, which become less marked following activation. The major treatment for severe botulism is advance medical and nursing supportive care with special attention to respiratory status.     

Wound botulism in heroin addiction]

Botulism is a rare disease which usually is caused by preformed botulinum toxin in food. However, this article describes a case of wound botulism in a 29-year-old male heroin addict who developed progressive diplopia, dysphagia and proximal weakness of skeletal limb muscles. He needed mechanical ventilation for two weeks. The clinical diagnosis of botulism was supported by neurophysiological tests. Assays for detection of botulinum toxin and Clostridium botulinum were negative. The patient had not eaten any contaminated food the last two weeks before symptoms appeared, but he had multiple contaminated skin wounds. After treatment with botulinum antitoxins and antibiotics he gradually recovered, and six weeks later he was discharged from hospital in good condition. To the best of our knowledge this is the first case of wound botulism reported in Norway.     

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.     

Temporary luminal arteriotomy seal for bypass grafting

OBJECTIVE: To compare the effects of botulinum toxin on static and dynamic aspects of eye movements, and thereby elucidate the mechanisms of its action on eye muscles. BACKGROUND: Laboratory evidence indicates that static alignment and saccades are subserved by different extraocular muscle fiber types, and botulinum toxin may cause specific dysfunction of the fibers controlling static alignment. Diplopia is a well-known side effect of periorbital botulinum toxin injections in humans, and may be a clinical correlate of the laboratory findings. METHODS: Search coil recording of eye movements was performed in one patient with systemic botulism, and in three patients with diplopia following periorbital injection of botulinum toxin A. RESULTS: In the patient with acute botulism, eye movement alignment, range, and saccadic velocity profiles were abnormal. In three patients with iatrogenic diplopia, static alignment was abnormal but movement range and saccadic velocities were within normal limits. Edrophonium improved the range of movements and saccadic velocities in the patient with systemic botulism but was ineffective in reversing ocular misalignment in the one iatrogenic patient to whom it was administered. CONCLUSIONS: Precise alignment is subserved by orbital singly innervated muscle fibers, and the effects of botulinum toxin are greatest on these fibers. This predilection is apparent when the toxin dose is very small, as must have been the case in our patients with iatrogenic diplopia. The lack of a response to edrophonium probably reflects structural damage to muscle fibers. In contrast, larger doses of toxin produce an acute dysfunction of all extraocular muscle fiber types, which is responsive to edrophonium and consequently reflects partial blockade at the neuromuscular junction.     

Aplasia cutis congenita: report of one case

CONTEXT: Shigella dysenteriae type 2 is rare in the United States, and outbreaks associated with this pathogen are uncommon. OBJECTIVE: To determine the magnitude and source of an outbreak of S dysenteriae type 2. DESIGN: Retrospective cohort. SETTING: Laboratory of a large medical center. PATIENTS: Case patients were identified as laboratory workers who had diarrhea on or after October 28 and a positive stool culture or temperature greater than 37.8 degrees C. Laboratory workers with diarrhea only were probable case patients. MAIN OUTCOME MEASURES: We interviewed laboratory staff and performed identification, serotyping, and pulsed-field gel electrophoresis on isolates from case patients, implicated food, and laboratory stock culture. RESULTS: From October 29 through November 1, a total of 12 (27%) of 45 laboratory staff developed severe, acute diarrheal illness; 8 had S dysenteriae isolated from stool and 4 were hospitalized. All case patients reported having eaten muffins or doughnuts placed in the staff break room on October 29. Pulsed-field gel electrophoresis showed stool isolates from 9 case patients were indistinguishable from S dysenteriae type 2 recovered from an uneaten muffin and from the laboratory's stock strain, a portion of which was missing. CONCLUSIONS: The source of the outbreak was most likely the laboratory's stock culture, which was used to contaminate the pastries. Results of this investigation underscore the need for adequate precautions to prevent inadvertent or intentional contamination from highly pathogenic laboratory specimens.     

Fibronectin in host defense: implications in the diagnosis, prophylaxis and therapy of infectious diseases

A polymerase chain reaction (PCR) was developed for the detection of Clostridium botulinum type A, a cause of human botulism. A two primer set and an oligonucleotide detection probe were used to specifically detect Cl. botulinum type A neurotoxin gene (BoNT/A). After 40 cycles of amplification, detection of a 798 bp amplified DNA fragment was carried out by agarose gel electrophoresis and Southern blot hybridization. This assay was able to detect 12.5 fg of purified target DNA or five bacteria per reaction. The sensitivity in artificially contaminated food samples after an 18 h enrichment step ranges from 10 to 10(3) bacteria per g according to the type of food samples. No cross-reactions were observed with the other Cl. botulinum toxinotypes and other bacteria found routinely in food. This PCR method may provide a suitable and rapid alternative to standard techniques for detection of Cl. botulinum type A in food samples.     

Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study

Consumers in the United States continue to eat raw or undercooked foods of animal origin despite public health warnings following several well-publicized outbreaks. We investigated an outbreak of Salmonella serotype Typhimurium infection in 158 patients in Wisconsin during the 1994 Christmas holiday period. To determine the vehicle and source of the outbreak, we conducted cohort and case-control studies, and environmental investigations in butcher shop A. Eating raw ground beef purchased from butcher shop A was the only item significantly associated with illness [cohort study: relative risk = 5.8, 95% confidence interval (CI) = 1.5-21.8; case control study: odds ratio = 46.2, 95% CI = 3.8-2751]. Inadequate cleaning and sanitization of the meat grinder in butcher shop A likely resulted in sustained contamination of ground beef during an 8-day interval. Consumer education, coupled with hazard reduction efforts at multiple stages in the food processing chain, will continue to play an important role in the control of foodborne illness.     

Mosaic type of the nontoxic-nonhemaggulutinin component gene in Clostridium botulinum type A strain isolated from infant botulism in Japan

The gene encoding the nontoxic-nonhemaggulutinin (NTNH) component was amplified by the PCR technique using two primer sets and the DNA template from Clostridium botulinum type A strain 7I03-H isolated from infant botulism in Japan. The nucleotide sequence revealed that the NTNH gene was composed of 1,193 amino acids with a molecular weight of 130868.08. Furthermore, the N-terminal half side and C-terminal half side of the NTNH component were similar to the NTNH component of type C and type A, respectively. These results indicate that the NTNH component gene codes the mosaic NTNH component composed of type A and type C. The hemaggulutinin gene, aha, and ORF-22 gene, orf-22a, were undetectable in the region upstream of the NTNH component gene, ant. Therefore, orf-22a is not thought to play a key role in the expression of botulinum type A progenitor toxin gene.     

Prognostic significance of hypertension and albuminuria for early mortality after acute myocardial infarction

The motile enterococci with the vanC gene have intrinsic low-level resistance to vancomycin, but have not been implicated in a nosocomial outbreak. We determined the colonization rate of motile enterococci in hospitalized and nonhospitalized patients. Perianal or stool specimens were cultured in Enterococcosel broth supplemented with 6 micrograms of vancomycin per mL. Rapid motility and pigment tests were performed on all enterococci isolated. A total of 82 motile and/or pigmented enterococci were isolated from 679 patients for a colonization rate of 12.1%. There were 43 Enterococcus gallinarum, 32 Enterococcus casseliflavus, 4 Enterococcus flavescens, and 3 Enterococcus mundtii identified. The E. gallinarum vancomycin MIC90 was 32 micrograms/mL and the E. casseliflavus vancomycin MIC90 was 8 micrograms/mL.     

Botulism after intake of half-fermented fish

From 1975 to 1997, 21 cases of foodborn botulism have been reported in Norway. Half-fermented fish is the major cause. We describe one patient with botulism following intake of home-prepared half-fermented fish. Seven people had eaten fish from the same bucket, but only two developed symptoms. The fish was initially stored at 13 degrees C; this probably explains why toxin developed. Type E toxin in moderate concentrations was found in fish samples. The patient was treated with specific antitoxin and made a gradual recovery. He returned to work after eight months.     

Use of botulinum toxin type F injections to treat torticollis in patients with immunity to botulinum toxin type A

Fifteen patients with torticollis who had been treated with repeated injections of botulinum toxin type A (botox A) developed antibodies to the toxin. This resulted in loss of benefit in the 13 patients who had improved with botox A injections and failure to develop muscle atrophy after injection in all 15 patients. Patients were then injected with botulinum toxin type F (botox F) in the same muscles that had been injected with botox A. Ten of the 15 improved after botox F injections, including 9 of the 12 patients who had improved with type A toxin. Six of 9 patients with pain had improvement in pain after botox F injections. Patients reported similar improvement with type F and type A toxins, but duration of benefit was approximately 3 months with type A and approximately 1 month with type F. Botox F is an effective treatment for torticollis in patients who are immune to botox A. The usefulness of type F toxin, however, is limited by short duration of benefit.     

Identification of random auditory waveforms. III. Effect of interference

A modified purification method was used to isolate the neurotoxin of proteolytic Clostridium botulinum type B strain Lamanna. The preparation was found to be a mixture of two protein forms. They were of molecular weight 152,000 and could not be separated by ion-exchange chromatography or electrophoresis in polyacrylamide gel. One was a single polypeptide chain, and the other was a dichain molecule (nicked toxin) held together by an interchain disulfide bond(s). Trypsinization increased the toxicity of the toxin preparation and converted the single-chain molecules into dichain forms that were indistinguishable from the endogenously generated nicked toxin. A protease of the type B culture, with substrate specificity similar to that of trypsin, did not change detectably the molecular form of unnicked type E toxin, although toxicity was increased. Higher toxicity was obtained when unnicked type E was trypsinized; the resulting preparation contained only nicked toxin molecules.     

Clinical features of infections due to Escherichia coli producing heat-stable toxin during an outbreak in Wisconsin: a rarely suspected cause of diarrhea in the United States

In September 1994, a foodborne outbreak of enterotoxigenic Escherichia coli (ETEC) infection occurred in attendees of a banquet in Milwaukee. E. coli was isolated from stool specimens from 13 patients that were comprehensively tested; isolates from five patients were positive for E. coli producing heat-stable toxin, were biochemically identified and serotyped as E. coli O153:H45, and were all resistant to tetracycline, ampicillin, sulfisoxazole, and streptomycin. Diarrhea (100%) and abdominal cramps (83%) were the most prevalent symptoms in 205 cases; vomiting (13%) and fever (19%) were less common. The median duration of diarrhea and abdominal cramps was 6 days and 5 days, respectively. In the United States, health care providers rarely consider ETEC as a possible cause of diarrhea in their patients, and few laboratories offer testing to identify ETEC. Hence, outbreaks of ETEC infection may be underdiagnosed and underreported. As in this outbreak, the relatively high prevalence of diarrhea and cramps lasting > or = 4 days and the low prevalence of vomiting and fever can help distinguish ETEC infection from Norwalk-like virus infection and gastroenteritis due to other causes with incubation times of > or = 15 hours and can provide direction for confirmatory laboratory testing.     

A 3D deformable surface model for segmentation of objects from volumetric data in medical images

Type A Clostridium botulinum, the causative agent of the food poisoning botulism disease, secretes botulinum neurotoxins along with seven neurotoxin associated proteins (NAPs). The function of NAPs has been shown to protect the neurotoxin from acidity, heat, and proteolytic attack in the environmental and gastrointestinal tract during the toxicogenesis of the botulism disease. One of the NAPs, purified from type A botulinum neurotoxin complex, showed hemagglutination activity. A direct interaction has been demonstrated between purified NAP, a 33-kDa hemagglutinin or Hn-33, and the neurotoxin by using Sephadex G-200 column chromatography. Furthermore, Hn-33 has complete resistance against proteolytic attack at pH 2.0 as well as at normal physiological pH. We have investigated digestion of the neurotoxin in the presence and absence of Hn-33. The neurotoxin alone has been found to be more susceptible to the enzymatic digestion than neurotoxin with Hn-33. The presence of Hn-33 changes the proteolytic fragmentation pattern of the neurotoxin. It seems that Hn-33 protects the neurotoxin from proteolysis either by structural modification of the neurotoxin or by blocking the protease accessible sites of the neurotoxin.     

Effect of ion implantation of TMA archwires on the rate of orthodontic sliding space closure

OBJECTIVE: A previous study of botulinum toxin type F (BTX-F) treatment for torticollis had shown a dose of 520 MU to be effective, but for a much shorter duration than is usual with botulinum toxin type A (BTX-A). The objective was to assess the effect of a higher dose of BTX-F. METHODS: Four of the previously treated patients, plus an additional patient, were treated with a higher dose of 780 MU BTX-F. All were secondary nonresponders to BTX-A due to neutralising antibodies. A test injection of 40 MU BTX-F was also given into the extensor digitorum brevis muscle (EDB), to examine the time course of the biological effect of the toxin electrophysiologically. Patients were followed up at two, four, eight, and 12 weeks. RESULTS: All patients reported subjective improvement lasting from seven to 11 (mean 8.6) weeks accompanied by a significant reduction in mean clinical severity scores at two weeks. Four patients had pain which was substantially reduced. The electrophysiological studies confirmed biological sensitivity to the toxin in all patients, showing a significant change beginning at two weeks and returning to baseline at 12 weeks. The time course of this effect paralleled roughly that of the clinical response. The four patients who had previously received 520 MU BTX-F reported that the response was better and longer in duration with 780 MU. Dysphagia was more common than reported with the lower dose. CONCLUSION: Better results are possible with higher doses of BTX-F but the duration of benefit is still shorter than with BTX-A, seemingly due to a shorter duration of neuromuscular junction blockade.     

Therapeutic use of botulinum A toxin in neurology

The highly potent neurotoxins produced by Clostridium botulinum lead to botulism when ingested in appreciable amounts. However, botulinum toxin injections delivered intramuscularly in very small quantities can produce a therapeutically intended focal paresis while producing only negligible local or systemic side effects. Over the past several years, various neurological disorders, especially those involving increased muscle tone and/or abnormal movements, have been successfully treated with local botulinum A toxin injections. The success of this method has led to a general change in the management of blepharospasm, torticollis spasmodicus, hemifacial spasm, and other disorders. Treatment is usually effective for 4 to 12 weeks; if symptoms recur, the injections can be repeated over a period of several years, usually with the same success. Side effects depend on the site of the injections, and are rare at the optimal dosage and always reversible. For optimum therapeutic results, this treatment must be restricted to specialized centers.     

Muscle fiber atrophy in leg muscles after botulinum toxin type A treatment of cervical dystonia

Previous electrophysiologic studies on the effects of local injections of botulinum toxin type A (BTX-A) have indicated impaired neuromuscular transmission in distant muscles. To further study possible distant effects of repeated BTX-A injections, we obtained percutaneous muscle biopsies of the vastus lateralis muscle from 11 patients with cervical dystonia. We examined the biopsies with histopathology and morphometry, and compared them with age-matched healthy controls. There was an increased frequency of angular atrophic type IIB fibers in the patient group, and the mean size of IIB fibers was significantly smaller (p < 0.05). In addition, there was a negative correlation between accumulated dose of botulinum toxin and relative size of type IIA fibers (p < 0.05). We postulate that the observed atrophy is due to distant effects of botulinum toxin causing progressive denervation-like changes in non-treated muscle. This observation calls for further, prospective studies of the long-term effects of the treatment.