[Botulism--actual epidemiologic and clinical problem].
Moniuszko, Anna; Czupryna, Piotr; Pancewicz, Sławomir Andrzej; Kondrusik, Maciej; Grygorczuk, Sambor; Zajkowska, Joanna Maria
2009-07-01
Botulism incidence in Poland is the highest in whole European Union. Polish emigrants suffer from botulism as well. This phenomenon is supposed to be caused by Polish custom of preparing home-made food. The most frequent clinical forms of botulism are: foodborne botulism, wound botulism and infant botulism. The diagnosis is mostly made on case history, physical examination and it is confirmed by toxin detection in food remains, vomits and stool. In treatment of adult's botulism antitoxin derived from hyperimmunizated horses, but in infant botulism human immunoglobulin should be used.
Clinical spectrum of botulism.
Cherington, M
1998-06-01
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.
Clinical mimics of infant botulism.
Francisco, Ann Marie O; Arnon, Stephen S
2007-04-01
Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992-1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998-2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The approximately 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation.
Foodborne botulism in a six-month-old infant caused by home-canned baby food.
Armada, Manuel; Love, Suzanne; Barrett, Elizabeth; Monroe, John; Peery, Dave; Sobel, Jeremy
2003-08-01
Previously reported cases of botulism in infants have been diagnosed as infant botulism; that is, botulism caused by intestinal colonization by Clostridium botulinum with intraluminal production and absorption of toxin. Foodborne botulism is caused by ingestion of preformed toxin. We describe an unusual case of foodborne botulism in a 6-month-old infant caused by the ingestion of improperly prepared home-canned baby food. This represents the youngest age of onset for foodborne botulism in the United States of which we are aware and illustrates the need to rule out foodborne botulism, which represents a public health emergency, regardless of the patient's age. The diagnosis could have been readily missed or delayed in this case because the weakness was rapidly progressive rather than insidious, as is typical of infant botulism.
Botulism mortality in the USA, 1975–2009
Jackson, Kelly A.; Mahon, Barbara E.; Copeland, John; Fagan, Ryan P.
2017-01-01
Botulism had mortality rates >60% before the 1950s. We reviewed confirmed botulism cases in the USA during 1975–2009 including infant, foodborne, wound, and other/unknown acquisition categories, and calculated mortality ratios. We created a multivariate logistic regression model for non-infant cases (foodborne, wound, and other/unknown). Overall mortality was 3.0% with 109 botulism-related deaths among 3,618 botulism cases [18 (<1%) deaths among 2,352 infant botulism cases, 61 (7.1%) deaths among 854 foodborne botulism cases, 18 (5.0%) deaths among 359 wound botulism cases, and 12 (22.6%) deaths among 53 other/unknown botulism cases]. Mortality among all cases increased with age; it was lowest among infants (0.8%) and highest among persons ≥80 years old (34.4%). Toxin type F had higher mortality (13.8%) than types A, B, or E (range, 1.4% to 4.1%). Efforts to reduce botulism mortality should target non-infant transmission categories and older adults. PMID:28603554
Falk, Absalom; Afriat, Amichay; Hubary, Yechiel; Herzog, Lior; Eisenkraft, Arik
2014-01-01
Infant botulism is a paralytic syndrome which manifests as a result of ingesting spores of the toxin secreting bacterium Clostridium botulinum by infants. As opposed to botulism in adults, treating infant botulism with horse antiserum was not approved due to several safety issues. This restriction has led to the development of Human Botulism Immune Globulin Intravenous (BIG-IV; sells under BabyBIG). In this article we review infant botulism and the advantages of treating it with BIG-IV.
Foodborne Botulism in the Republic of Georgia
Katsitadze, Guram; Moiscrafishvili, Maia; Zardiashvili, Tamar; Chokheli, Maia; Tarkhashvili, Natalia; Jhorjholiani, Ekaterina; Chubinidze, Maia; Kukhalashvili, Teimuraz; Khmaladze, Irakli; Chakvetadze, Nelli; Imnadze, Paata; Sobel, Jeremy
2004-01-01
Foodborne botulism is a potentially fatal, paralytic illness that can cause large outbreaks. A possible increase in botulism incidence during 2001 in the Republic of Georgia prompted this study. We reviewed surveillance data and abstracted records of patients with botulism who were hospitalized from 1980 to 2002. During this period, 879 botulism cases were detected. The median annual incidence increased from 0.3 per 100,000 during 1980 to 1990 to 0.9 per 100,000 during 1991 to 2002. For 706 botulism patients hospitalized from 1980 to 2002, 80% of their cases were attributed to home-preserved vegetables. Surveillance evaluation verified that botulism incidence varied greatly by region. Georgia has the highest nationally reported rate of foodborne botulism in the world. A strategy addressing individual behaviors in the home is needed to improve food safety; developing this strategy requires a deeper understanding of why botulism has increased and varies by region. PMID:15498162
Botulism in the United States: a clinical and epidemiologic review.
Shapiro, R L; Hatheway, C; Swerdlow, D L
1998-08-01
Botulism is caused by a neurotoxin produced from the anaerobic, spore-forming bacterium Clostridium botulinum. Botulism in humans is usually caused by toxin types A, B, and E. Since 1973, a median of 24 cases of foodborne botulism, 3 cases of wound botulism, and 71 cases of infant botulism have been reported annually to the Centers for Disease Control and Prevention (CDC). New vehicles for transmission have emerged in recent decades, and wound botulism associated with black tar heroin has increased dramatically since 1994. Recently, the potential terrorist use of botulinum toxin has become an important concern. Botulism is characterized by symmetric, descending, flaccid paralysis of motor and autonomic nerves, usually beginning with the cranial nerves. Blurred vision, dysphagia, and dysarthria are common initial complaints. The diagnosis of botulism is based on compatible clinical findings; history of exposure to suspect foods; and supportive ancillary testing to rule out other causes of neurologic dysfunction that mimic botulism, such as stroke, the Guillain-Barré syndrome, and myasthenia gravis. Laboratory confirmation of suspected cases is performed at the CDC and some state laboratories. Treatment includes supportive care and trivalent equine antitoxin, which reduces mortality if administered early. The CDC releases botulism antitoxin through an emergency distribution system. Although rare, botulism outbreaks are a public health emergency that require rapid recognition to prevent additional cases and to effectively treat patients. Because clinicians are the first to treat patients in any type of botulism outbreak, they must know how to recognize, diagnose, and treat this rare but potentially lethal disease.
Ikeguchi, Kunihiko
2011-07-01
Botulism is a rare but potentially life-threatening motor and autonomic paralytic syndrome caused by the action of neurotoxins released by Clostridium botulinum. The modern syndromes of botulism have 6 forms: 4 naturally occurring syndromes and 2 human-induced syndromes. Food-borne botulism is caused by ingestion of foods contaminated with botulinum toxin. Wound botulism is caused by C. botulinum infection of a wound and in situ toxin production. Infant botulism and adult intestinal botulism are caused by intestinal colonization and in situ toxin production. Air-borne botulism results from aerosolization of botulinum toxin, whereas iatrogenic botulism occurs due to injection of a large dose of the toxin. Another human-induced form may occur when the aerosolized toxin is released as an act of bioterrorism. All forms of botulism produce a similar syndrome: symmetrical cranial motor nerve palsies followed by descending, symmetrical motor weakness, which may progress to respiratory failure requiring intubation and respiratory support. The clinical diagnosis can be confirmed by electrophysiological studies. Laboratory diagnosis includes serum analysis of toxin by bioassay in mice. Analysis of stool, vomitus, and suspected food items may reveal the toxin. In wound botulism, isolation of C. botulinum from the wound site is diagnostic. The mainstays of therapy are meticulous intensive care including respiratory support, when necessary, and timely administration of the antitoxin.
Nakamura, Yuko; Sawada, Mikio; Ikeguchi, Kunihiko; Nakano, Imaharu
2012-08-01
Botulism is a neuroparalytic disease caused by neurotoxins produced by Clostridium botulinum, and classically presents as palsies of cranial nerves and acute descending flaccid paralysis. Food-borne botulism is the most common form of botulism, and caused by preformed neurotoxins produced by Clostridium botulinum. Electrophysiological studies play an important role in the early diagnosis. Confirmation of the diagnosis is based on the detection of botulinum toxins in the patient's serum or stool. In Japan, decades ago, botulism type E occurred, though only sporadically, almost every year, but in recent years, has dramatically decreased in frequency. Botulism is a curable disease when treated early and adequately. Differential diagnosis of cranial nerves and limb muscle palsies with rapid exacerbation should include food-borne botulism.
Lai, Lung-Shiang; Wang, Yi-Mei; Lin, Chin-Hsien
2011-06-01
Botulism type E intoxication is a rare condition among human botulism. We aim to describe a first case of botulism type E intoxication in Taiwan. We report a 36-year-old young man with foodborne botulism type E associated with commercially vacuum packaged dried bean curd. He developed bilateral ptosis, diplopia and dysphagia 4 days after taking the dried bean curd. Electrophysiologic findings demonstrated waxing responses to 3 Hz repetitive nerve stimulation and decreased compound muscle action potentials on peripheral nerve conduction study. A bioassay for botulism in mice demonstrated that the patient had botulism caused by type E botulinum toxin. Antibodeis to C. botulinum type E were identified from his serum, confirming the diagnosis. This is the first known case of foodborne type E botulism in Taiwan. The potential source of this foodborne botulism should consider contaminated food made of soy beans.
Food-borne botulism: still actual topic.
Brola, Waldemar; Fudala, Malgorzata; Gacek, Szymon; Gruenpeter, Pawel
2013-02-06
Even though since the mid-1990s the number of food-borne botulism cases has systematically decreased and it now occurs in Poland relatively rarely, it is still a real epidemiological problem. There are about 30 cases of botulism in Poland a year, which ranks Poland the first among the European Union. In most cases the symptomatology of botulism is typical, however it does not always fully coincide with the one described in medical manuals which emphasise the dramatic clinical course of botulism with its frequent fatal consequences. Diagnosis of botulism may be difficult because of its rare prevalence and a variable clinical course, especially in old patients. Authors of this paper describe two cases of botulism and diagnostic problems associated with it.
Food-borne botulism: still actual topic
Brola, Waldemar; Fudala, Malgorzata; Gacek, Szymon; Gruenpeter, Pawel
2013-01-01
Even though since the mid-1990s the number of food-borne botulism cases has systematically decreased and it now occurs in Poland relatively rarely, it is still a real epidemiological problem. There are about 30 cases of botulism in Poland a year, which ranks Poland the first among the European Union. In most cases the symptomatology of botulism is typical, however it does not always fully coincide with the one described in medical manuals which emphasise the dramatic clinical course of botulism with its frequent fatal consequences. Diagnosis of botulism may be difficult because of its rare prevalence and a variable clinical course, especially in old patients. Authors of this paper describe two cases of botulism and diagnostic problems associated with it. PMID:23391950
Infant botulism: review and clinical update.
Rosow, Laura K; Strober, Jonathan B
2015-05-01
Botulism is a rare neuromuscular condition, and multiple clinical forms are recognized. Infant botulism was first identified in the 1970s, and it typically occurs in infants younger than 1 year of age who ingest Clostridium botulinum spores. A specific treatment for infant botulism, intravenous botulism immunoglobulin (BIG-IV or BabyBIG®), was developed in 2003, and this treatment has substantially decreased both morbidity and hospital costs associated with this illness. This article will review the pathogenesis of infant botulism as well as the epidemiology, clinical manifestations, diagnosis, and treatment of this condition. Copyright © 2015 Elsevier Inc. All rights reserved.
Notes from the field: botulism from drinking prison-made illicit alcohol - Arizona, 2012.
2013-02-08
During November 24-27, 2012, the Arizona Department of Health Services (ADHS) was notified that eight male inmates of prison A, a maximum security prison, had been hospitalized for treatment of an acute neurologic condition suspected to be botulism. Botulism is a serious paralytic illness caused by a nerve toxin produced by the bacterium Clostridium botulinum. All eight patients reported drinking pruno, an illicitly brewed alcoholic beverage that has been associated with botulism outbreaks in prisons. This was the second outbreak of botulism in prison A during 2012; in August, four inmates were hospitalized for botulism after drinking pruno. Pinal County Health Services (PCHS), ADHS, and CDC investigated to identify the outbreak source, learn about pruno production, and provide recommendations for preventing future outbreaks of botulism in prisons.
Foodborne botulism treated with heptavalent botulism antitoxin.
Hill, Stanley E; Iqbal, Raza; Cadiz, Christine L; Le, Jennifer
2013-02-01
To report a case of foodborne botulism and subsequent use of the investigational heptavalent botulism antitoxin (H-BAT). A 60-year-old man was hospitalized with blurred vision, diplopia, and dysarthria. On hospital day 2, the patient was transferred to the intensive care unit for progressive fatigable weakness with ptosis, dysphagia, dysarthria, and nausea. Secondary to worsening respiratory distress, the patient was intubated and placed on a ventilator. The patient could open his eyes only with assistance but still had normal strength in all extremities. H-BAT was administered 48 hours after presentation for possible botulism. The patient then revealed that he consumed home-canned corn several days prior to admission. On hospital day 8, botulinum neurotoxin was confirmed in the patient's serum and the home-canned corn. The patient slowly regained muscle strength and was discharged to a long-term acute care facility on hospital day 22. Foodborne botulism is caused by a neurotoxin from Clostridium botulinum and usually occurs after the consumption of improperly prepared home-canned food. Botulism is characterized by symmetrical descending paralysis that may progress to respiratory arrest. The standard confirmatory test for botulism is a mouse bioassay to prove the presence of botulinum neurotoxin. Outside of supportive care, the treatment options for botulism are limited. Individuals with botulism often require intensive care unit monitoring and potentially ventilatory support. H-BAT, the only treatment available for botulism in patients older than 1 year, is a purified and despeciated equine-derived immunoglobulin active against all known botulinum neurotoxins. H-BAT's despeciation significantly reduces the risk of hypersensitivity reactions, anaphylaxis, and serum sickness. In a confirmed case of foodborne botulism treated with H-BAT, the patient tolerated H-BAT and did not develop any hypersensitivity reactions or serum sickness.
Botulism in Italy, 1986 to 2015
Anniballi, Fabrizio; Auricchio, Bruna; Fiore, Alfonsina; Lonati, Davide; Locatelli, Carlo Alessandro; Lista, Florigio; Fillo, Silvia; Mandarino, Giuseppina; De Medici, Dario
2017-01-01
Botulism is a rare but severe neuroparalytic disease caused by botulinum toxins. Because of its high potential impact on public health, botulism is a closely monitored communicable disease in Europe. In Italy, which has one of the highest incidence rates in Europe (0.03 cases per 100,000 population), botulism is monitored through a case-based passive surveillance system: the front-line physician who diagnoses a suspected case must notify the Local Health Units immediately, and the Ministry of Health's office within 12 hours. From 1986 to 2015, 466 confirmed cases of botulism were recorded in Italy (of 1,257 suspected cases). Of these, 421 were food-borne (the most frequently seen form of botulism due to the consumption of improperly home-canned foods), 36 were infant botulism, which accounts for ca 50% of all these types of cases registered in Europe, six were wound-related and three were due to adult intestinal colonisation. This scenario suggests that stronger efforts should be made towards raising public awareness of the risk of food-borne botulism, especially with respect to home-preserved foods, as well as improving the training of front-line medical personnel, to ensure that a quick and accurate diagnosis of botulism can be made. PMID:28661393
Gregory, A R; Ellis, T M; Jubb, T F; Nickels, R J; Cousins, D V
1996-02-01
The development of specific enzyme-linked immunosorbent assays (ELISA) for antibody to types C and D Clostridium botulinum toxins for investigation of botulism in cattle is described. Partially purified type C and D toxins were used as antigens to develop these ELISAs. Specificity of the ELISAs was evaluated on sera from 333 adult beef and dairy cattle from areas with no history or evidence of botulism in animals or water birds. The test was also evaluated on sera from 41 herds that included herds vaccinated against botulism, confirmed botulism cases and herds from areas where the disease is considered endemic. The ELISAs detected the presence of antibody to botulinum toxins in samples from vaccinated cattle and both convalescent and clinically normal animals from unvaccinated herds with outbreaks of botulism. Antibody was also found in unvaccinated animals from herds in which there had been no diagnosed botulism cases in areas where botulism was considered endemic. Sera from some unvaccinated cattle with high ELISA reactivity was shown to be protective for mice in botulinum toxin neutralisation tests. The use of these tests in investigations of botulism in cattle is discussed.
Asymmetric type F botulism with cranial nerve demyelination.
Filozov, Alina; Kattan, Jessica A; Jitendranath, Lavanya; Smith, C Gregory; Lúquez, Carolina; Phan, Quyen N; Fagan, Ryan P
2012-01-01
We report a case of type F botulism in a patient with bilateral but asymmetric neurologic deficits. Cranial nerve demyelination was found during autopsy. Bilateral, asymmetric clinical signs, although rare, do not rule out botulism. Demyelination of cranial nerves might be underrecognized during autopsy of botulism patients.
Asymmetric Type F Botulism with Cranial Nerve Demyelination
Kattan, Jessica A.; Jitendranath, Lavanya; Smith, C. Gregory; Lúquez, Carolina; Phan, Quyen N.; Fagan, Ryan P.
2012-01-01
We report a case of type F botulism in a patient with bilateral but asymmetric neurologic deficits. Cranial nerve demyelination was found during autopsy. Bilateral, asymmetric clinical signs, although rare, do not rule out botulism. Demyelination of cranial nerves might be underrecognized during autopsy of botulism patients. PMID:22257488
First Report Worldwide of an Infant Botulism Case Due to Clostridium botulinum Type E▿
Lúquez, Carolina; Dykes, Janet K.; Yu, Patricia A.; Raphael, Brian H.; Maslanka, Susan E.
2010-01-01
Clostridium botulinum type E has been associated with botulism in adults but never in infants. Infant botulism type E cases have been associated with neurotoxigenic strains of C. butyricum. We report the first infant botulism case due to C. botulinum type E worldwide. PMID:19906896
Botulism with Unusual Rapid Progression to Complete Paralysis in a Child.
Tsai, Hui-Ju; Liang, Wen-Chen; Wang, Chien-Hua; Chou, Po-Ching; Hsu, Jong-Hau; Huang, Chia-Tsuan; Jong, Yuh-Jyh
2015-12-01
Botulism is a severe neuroparalytic illness which is difficult to diagnose accurately, especially in children. We report a child with type A botulism intoxication, with very rapid progression to coma-like consciousness and respiratory failure. Careful physical examinations led to the suspicion of botulism, and electrophysiologic examinations, including electroencephalogram and repetitive nerve stimulation tests, further supported the diagnosis. Hospitalization due to botulism had a great emotional impact on the patient and psychological support was crucial. Copyright © 2013. Published by Elsevier B.V.
Infant botulism and indications for administration of botulism immune globulin.
Pifko, Elysha; Price, Amanda; Sterner, Sarah
2014-02-01
Infant botulism is caused by the ingestion of Clostridium botulinum spores and leads to a life-threatening descending motor weakness and flaccid paralysis in infant children. This disease presents with symptoms such as constipation, weakness, and hypotonia and can lead to respiratory failure. Botulism immune globulin (BIG) was created to treat this deadly disease and functions by neutralizing all systemically circulating botulism toxins. It is indicated in children with clinically diagnosed infant botulism, before diagnostic confirmation, and has been shown to lead to a significant reduction in intensive care unit and hospital stay for these patients. This review article discusses the epidemiology, clinical presentation, history of BIG, and indications for administration of BIG.
Wound botulism acquired in the Amazonian rain forest of Ecuador.
Reller, Megan E; Douce, Richard W; Maslanka, Susan E; Torres, Darwin S; Manock, Stephen R; Sobel, Jeremy
2006-04-01
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.
A case of botulism in New Zealand.
Smyth, Duncan; Deverall, Eamonn; Balm, Michelle; Nesdale, Annette; Rosemergy, Ian
2015-11-20
We describe the first case of food-borne botulism seen in New Zealand for 30 years. Botulism is an important diagnosis to consider in a patient with rapidly progressive descending paralysis and normal sensorium. Early recognition, timely institution of intensive care support and administration of botulism antitoxin are the most important aspects of management.
Lafrancois, Brenda Moraska; Riley, Stephen C.; Blehert, David S.; Ballmann, Anne E.
2011-01-01
Relationships between large-scale environmental factors and the incidence of type E avian botulism outbreaks in Lake Michigan were examined from 1963 to 2008. Avian botulism outbreaks most frequently occurred in years with low mean annual water levels, and lake levels were significantly lower in outbreak years than in non-outbreak years. Mean surface water temperatures in northern Lake Michigan during the period when type E outbreaks tend to occur (July through September) were significantly higher in outbreak years than in non-outbreak years. Trends in fish populations did not strongly correlate with botulism outbreaks, although botulism outbreaks in the 1960s coincided with high alewife abundance, and recent botulism outbreaks coincided with rapidly increasing round goby abundance. Botulism outbreaks occurred cyclically, and the frequency of outbreaks did not increase over the period of record. Climate change scenarios for the Great Lakes predict lower water levels and warmer water temperatures. As a consequence, the frequency and magnitude of type E botulism outbreaks in the Great Lakes may increase.
Botulism in Italy, 1986 to 2015.
Anniballi, Fabrizio; Auricchio, Bruna; Fiore, Alfonsina; Lonati, Davide; Locatelli, Carlo Alessandro; Lista, Florigio; Fillo, Silvia; Mandarino, Giuseppina; De Medici, Dario
2017-06-15
Botulism is a rare but severe neuroparalytic disease caused by botulinum toxins. Because of its high potential impact on public health, botulism is a closely monitored communicable disease in Europe. In Italy, which has one of the highest incidence rates in Europe (0.03 cases per 100,000 population), botulism is monitored through a case-based passive surveillance system: the front-line physician who diagnoses a suspected case must notify the Local Health Units immediately, and the Ministry of Health's office within 12 hours. From 1986 to 2015, 466 confirmed cases of botulism were recorded in Italy (of 1,257 suspected cases). Of these, 421 were food-borne (the most frequently seen form of botulism due to the consumption of improperly home-canned foods), 36 were infant botulism, which accounts for ca 50% of all these types of cases registered in Europe, six were wound-related and three were due to adult intestinal colonisation. This scenario suggests that stronger efforts should be made towards raising public awareness of the risk of food-borne botulism, especially with respect to home-preserved foods, as well as improving the training of front-line medical personnel, to ensure that a quick and accurate diagnosis of botulism can be made. This article is copyright of The Authors, 2017.
Newkirk, Ryan W; Hedberg, Craig W
2012-02-01
The main objective of this study was to develop an understanding of the descriptive epidemiology of foodborne botulism in the context of outbreak detection and food defense. This study used 1993-2008 data from the Centers for Disease Control and Prevention (CDC) Annual Summaries of Notifiable Diseases, 2003-2006 data from the Bacterial Foodborne and Diarrheal Disease National Case Surveillance Annual Reports, and 1993-2008 data from the Annual Listing of Foodborne Disease Outbreaks. Published outbreak investigation reports were identified through a PubMed search of MEDLINE citations for botulism outbreaks. Fifty-eight foodborne botulism outbreaks were reported to CDC between 1993 and 2008. Four hundred sixteen foodborne botulism cases were documented; 205 (49%) were associated with outbreaks. Familial connections and co-hospitalization of initial presenting cases were common in large outbreaks (>5 cases). In these outbreaks, the time from earliest exposure to outbreak recognition varied dramatically (range, 48-216 h). The identification of epidemiologic linkages between foodborne botulism cases is a critical part of diagnostic evaluation and outbreak detection. Investigation of an intentionally contaminated food item with a long shelf life and widespread distribution may be delayed until an astute physician suspects foodborne botulism; suspicion of foodborne botulism occurs more frequently when more than one case is hospitalized concurrently. In an effort to augment national botulism surveillance and antitoxin release systems and to improve food defense and public health preparedness efforts, medical organizations and Homeland Security officials should emphasize the education and training of medical personnel to improve foodborne botulism diagnostic capabilities to recognize single foodborne botulism cases and to look for epidemiologic linkages between suspected cases.
First Report of an Infant Botulism Case Due to Clostridium botulinum Type Af
de Jong, Laura I. T.; Fernández, Rafael A.; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R.; Dykes, Janet K.
2014-01-01
Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide. PMID:25502535
Burningham, M D; Walter, F G; Mechem, C; Haber, J; Ekins, B R
1994-12-01
Wound botulism is a rare infectious and toxicologic complication of trauma and i.v. drug abuse. Only 39 cases have been reported in detail in the English literature. This case report describes a patient with wound botulism who presented to four medical facilities before receiving definitive diagnosis and treatment. Although his history and physical examination were consistent with wound botulism, diagnosis and therapy were delayed because this rare disease was not considered initially in the differential diagnosis. Wound botulism should be considered in trauma patients and i.v. drug abusers who present with cranial nerve palsies and descending paresis.
Infantile botulism: pitfalls in electrodiagnosis.
Sheth, R D; Lotz, B P; Hecox, K E; Waclawik, A J
1999-03-01
Botulism in infants, unless recognized early, is associated with high mortality and morbidity. The diagnosis is suspected when infants present with sudden onset of weakness, respiratory failure, and constipation and is confirmed by demonstration of botulinum toxin in stool several weeks later. Electrodiagnosis allows quick and reliable confirmation of botulism. Low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and the absence of post-tetanic exhaustion support the diagnosis. Two infants with confirmed botulism did not exhibit the characteristic electrodiagnostic features, demonstrating the pitfalls in electrodiagnosis of infantile botulism.
An outbreak of foodborne botulism in Ontario
Loutfy, Mona R; Austin, John W; Blanchfield, Burke; Fong, Ignatius W
2003-01-01
Botulism is a rare paralytic illness resulting from a potent neurotoxin produced by Clostridium botulinum. Botulism in Canada is predominately due to C botulinum type E and affects mainly the First Nations and Inuit populations. The most recent outbreak of botulism in Ontario was in Ottawa in 1991 and was caused by C botulinum type A. We report an outbreak of foodborne type B botulism in Ontario, which implicated home-canned tomatoes. The outbreak was characterized by mild symptoms in two cases and moderately severe illness in one case. The investigation shows the importance of considering the diagnosis of botulism in patients presenting with cranial nerve and autonomic dysfunction, especially when combined with gastrointestinal complaints; it also highlights the importance of proper home canning technique. PMID:18159458
Global occurrence of infant botulism, 1976-2006.
Koepke, Ruth; Sobel, Jeremy; Arnon, Stephen S
2008-07-01
To summarize the worldwide occurrence of reported infant (intestinal toxemia) botulism cases since first recognition of the disease in 1976. We collected information on infant botulism cases by active and passive surveillance, by provision of therapeutic Human Botulism Immune Globulin to suspected cases, and by searching the medical literature. We defined a case as laboratory-confirmed botulism that occurred in an infant
... bacterium called Clostridium botulinum. It occurs naturally in soil. There are several kinds of botulism. Foodborne botulism ... baby consumes the spores of the bacteria from soil or honey. All forms can be deadly and ...
Infant botulism: advice on avoiding feeding honey to babies and other possible risk factors.
Grant, Kathie A; McLauchlin, Jim; Amar, Corinne
2013-07-01
Botulism is a rare, but extremely serious, disease and Public Health England is responsible for its diagnosis and surveillance in the UK. Over the past five years (2008-2013), the most common form of the disease recognised in the UK has been infant botulism. The aim of this article is to raise awareness of infant botulism and highlight advice for parents and carers of infants that honey should not be fed to infants under 12 months old. Other possible risk factors for infant botulism are also discussed in this article, including household pet reptiles and herbal teas.
New targets in the search for preventive and therapeutic agents for botulism.
Anniballi, Fabrizio; Lonati, Davide; Fiore, Alfonsina; Auricchio, Bruna; De Medici, Dario; Locatelli, Carlo Alessandro
2014-09-01
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.
Diplopia as the primary presentation of foodborne botulism.
Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K; Moshirfar, Majid
2012-05-01
Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist.
Diplopia as the primary presentation of foodborne botulism
Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K.; Moshirfar, Majid
2012-01-01
Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist. PMID:22993467
First report of an infant botulism case due to Clostridium botulinum type Af.
de Jong, Laura I T; Fernández, Rafael A; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R; Dykes, Janet K; Lúquez, Carolina
2015-02-01
Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
... know that these spores can be found in honey. Do not feed honey to children younger than 12 months because it ... Wound botulism also has been reported following traumatic injuries, such as motorcycle crashes and surgeries. About Botulism ...
Nakamura, Yuko; Sawada, Mikio; Ikeguchi, Kunihiko; Nakano, Imaharu
2011-09-01
Botulism is a neuroparalytic disease caused by neurotoxins produced by Clostridium botulinum. Food-borne botulism is a kind of exotoxin-caused food intoxication. Although this disease is rarely reported in Japan now, it is a cause of great concern because of its high mortality rate, and botulism cases should be treated as a public health emergency. Botulism classically presents as acute symmetrical descending flaccid paralysis. Its diagnosis is based on the detection of botulinum toxins in the patient's serum or stool specimens. Electrophysiologic tests of such patients show reduced compound muscle action potentials (CMAPs), low amplitudes and short durations of motor unit potentials (MUPs), and mild waning in repetitive low-frequency stimulations. Single fiber electromyography (EMG) is particularly useful for the diagnosis of botulism. We report a case of food-borne botulism that we had encountered. An 83-year-old man with rapidly progressive diplopia, dysphagia, and tetraplegia was hospitalized; he required intensive care, including artificial ventilatory support. Electrophysiologic tests yielded findings compatible with botulism. We made a clinical diagnosis of food-borne botulism and administered antitoxin on the seventh disease day. The patient's motor symptoms started ameliorating several days after the antitoxin injection. Subsequently, botulinum toxin type A was detected in the patient's serum specimen by using a bioassay, and the type A gene and silent B gene were detected in his serum specimen by using polymerase chain reaction (PCR). C. botulinum was also obtained from stool culture on the 17th and 50th disease days. Botulism is a curable disease if treated early. Although it is a rare condition, it should always be considered in the differential diagnosis of patients with rapid onset of cranial nerve and limb muscle palsies.
Accuracy of a Mouse Bioassay for the Diagnosis of Botulism in Horses.
Johnson, A L; McAdams-Gallagher, S C; Aceto, H
2016-07-01
The laboratory diagnosis of botulism in horses traditionally has relied upon the mouse bioassay (MBA). The accuracy of this test for the diagnosis of botulism in horses is unknown. Our goal was to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the MBA on laboratory-processed fecal and gastrointestinal samples for foals and adult horses. Cases included all horses with a final clinical diagnosis of botulism that were admitted between 1986 and 2011 and had MBA testing performed. Controls included horses without botulism that were admitted during the same time period and had MBA testing performed. Retrospective study. Horses suspected of having botulism had fecal or (less commonly) gastrointestinal content samples tested using MBA. For every hospitalized botulism suspect, control samples were obtained from ≥1 additional hospitalized horses not suspected to have botulism. One hundred and twenty-nine adult horses and 253 adult controls were identified. Overall sensitivity of the MBA was only 32% but specificity was 97%. Forty-three foal cases and 21 foal controls were evaluated; sensitivity of the MBA was 53% and specificity was 100%. Positive predictive value was substantially higher (100% for foals and 89% for adults) than negative predictive value (51% for foals and 67% for adults). Mouse bioassay has low sensitivity but high specificity for the diagnosis of botulism in horses. Positive results are highly suggestive of botulism but negative results do not exclude the diagnosis. Unaffected horses and foals rarely shed C. botulinum in their feces. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Yasmin, Seema; Adams, Laura; Briggs, Graham; Weiss, Joli; Bisgard, Kris; Anderson, Shoana; Tsang, Clarisse; Henke, Evan; Vasiq, Muhammad; Komatsu, Ken
2015-10-01
The authors investigated the second botulism outbreak to occur in a maximum security prison in Arizona within a 4-month period. Botulism was confirmed in eight men aged 20 to 35 years who reported sharing a single batch of pruno made with potatoes. Initial symptoms included blurred vision, slurred speech, muscle weakness, ptosis, and dysphagia. All patients received heptavalent botulinum antitoxin, seven required mechanical ventilation, and all survived. The median incubation period was 29 hours. Sera from all patients and leftover pruno tested positive for botulinum toxin type A. Botulism should be considered among prisoners with cranial nerve palsies and descending, symmetric flaccid paralysis. Prison-brewed alcohol, particularly when made with potatoes, can be a vehicle for botulism and is associated with outbreaks of botulism in prisons. © The Author(s) 2015.
Botulism in children: a diagnostic dilemma in developing countries.
Khan, Muhammad Rehan; Maheshwari, Prem Kumar; Ibrahim, Shahnaz Hamid; Haque, Anwarul
2013-06-01
Botulism is a well-known disease of the neuromuscular junction. It is a rare but curable cause of paralysis in paediatric population. In addition to classical clinical signs and symptoms, the diagnosis of botulism requires laboratory confirmation of intoxication by various biological tests. These include demonstration of botulinum toxin in serum or isolation of the Clostridium botulinum from stool/gastric aspirates. However, it is not always possible to confirm intoxication due to unavailability of technical facilities, especially in resource limited countries like Pakistan. Under these circumstances, electrophysiological studies serve as an excellent diagnostic tool. These studies can provide quick diagnosis of botulism so that early administration of botulism immunoglobulin, if available, can reduce morbidity, mortality and length of stay in hospital. We report a case of botulism from Pakistan diagnosed on the basis of electrophysiological studies.
First Case of Infant Botulism Caused by Clostridium baratii Type F in California
Barash, Jason R.; Tang, Tania W. H.; Arnon, Stephen S.
2005-01-01
In late 2003 a severely hypotonic neonate, just 38 h old at onset of illness, was found to have infant botulism caused by neurotoxigenic Clostridium baratii type F. Environmental investigations failed to identify a source of this strain. This is the youngest patient reported to have infant botulism and the fifth instance of infant botulism caused by C. baratii type F. PMID:16082001
Fenicia, Lucia; Anniballi, Fabrizio
2009-01-01
Infant botulism is a rare disease that affects infant less than 12 months of age. The illness results from absorption of botulinum toxin produced in situ by neurotoxigenic clostridia that can temporarily colonize the intestinal tract of infants. To date, all inhabited continents except Africa have reported cases of infant botulism. Recognition of cases seem directly related to physician awareness and clinical suspicion. This review summarizes microbiological, clinical and epidemiological features of infant botulism.
Use of sentinel mallards for epizootiologic studies of avian botulism
Rocke, T.E.; Brand, C.J.
1994-01-01
Captive-reared mallards (Anas platyrhynchos) were used as sentinels to study the epizootiology of avian botulism at the Sacramento National Wildlife Refuge, Willows, California (USA) from 1986 to 1989. Sentinel mallards were wing-clipped, and 40 to 50 birds were confined in 1.6-ha enclosures in 11 selected wetlands (pools). Enclosures were searched intensively three to four times weekly from July through October. Sick and dead wild and sentinel birds were collected, necropsied, and tested for type C botulism toxin. Botulism epizootics occurred in sentinel mallards in 1986, 1987, and 1989, but only a few isolated cases of botulism were detected in 1988. In most epizootics, botulism also was detected simultaneously in wild birds using the same pool outside the enclosure. Epizootics in sentinels were initiated and perpetuated in the absence of vertebrate carcasses. A sex-specific trend in the probability of intoxication was detected, with males contracting botulism at a higher rate than females. Daily mortality rates of sentinels during botulism epizootics ranged from 0.0006 to 0.0600, with a mean of 0.0190. These rates would result in the daily loss of 0.6 to 60 birds per thousand at risk. The use of sentinel birds provided an effective means of gathering site-specific epizootiologic data.
Water and sediment characteristics associated with avian botulism outbreaks in wetlands
Rocke, Tonie E.; Samuel, Michael D.
1999-01-01
Avian botulism kills thousands of waterbirds annually throughout North America, but management efforts to reduce its effects have been hindered because environmental conditions that promote outbreaks are poorly understood. We measured sediment and water variables in 32 pairs of wetlands with and without a current outbreak of avian botulism. Wetlands with botulism outbreaks had greater percent organic matter (POM) in the sediment (P = 0.088) and lower redox potential in the water (P = 0.096) than paired control wetlands. We also found that pH, redox potential, temperature, and salinity measured just above the sediment-water interface were associated (P ≤ 0.05) with the risk of botulism outbreaks in wetlands, but relations were complex, involving nonlinear and multivariate associations. Regression models indicated that the risk of botulism outbreaks increased when water pH was between 7.5 and 9.0, redox potential was negative, and water temperature was >20°C. Risk declined when redox potential increased (>100), water temperature decreased (10-15°C), pH was 9.0, or salinity was low (<2.0 ppt). Our predictive models could allow managers to assess potential effects of wetland management practices on the risk of botulism outbreaks and to develop and evaluate alternative management strategies to reduce losses from avian botulism.
[Clostridia: toxin masters. Botulism: from botox to sausages?].
Buzzi, Marta; Rossel, Anne; Coen, Matteo; Kaiser, Laurent; Abbas, Mohamed
2016-04-13
Clostridia are ubiquitous Gram-positive bacteria whose toxins are responsible for serious diseases. In this article we report a case of foodborne botulism we have recently managed. Moreover, we briefly describe the major clinical syndromes caused by different species of Clostridium (except for C. difficile infections, as this subject has been previously extensively reviewed in this journal). Botulism causes a flaccid paralysis starting with cranial nerves. Administration of botulism anti-toxin should be rapidly considered as soon as botulism is suspected, as prognosis is largely dependent on timely treatment; alerting the public health authorities is equally important. In Switzerland botulinum antitoxin can be obtained from the pharmacy of the Swiss Army.
Infant botulism, type F, presenting at 54 hours of life.
Keet, Corinne A; Fox, Christine K; Margeta, Marta; Marco, Elysa; Shane, Andi L; Dearmond, Stephen J; Strober, Jonathan B; Miller, Steven P
2005-03-01
We report a case of botulism in a 54-hour-old infant with rapidly progressive fulminant paralysis and rapid spontaneous recovery atypical for infant botulism. Clostridium baratii and type F botulinum neurotoxin were isolated from the patient's stool. This unique presentation with rapid recovery is consistent with pharmacokinetics of type F botulinum neurotoxin. Interestingly, a muscle biopsy also revealed pathologic changes early in the disease course. This article reports the youngest known case of infant botulism and only the third reported case of this disease caused by type F neurotoxin. Botulism should be considered in patients of any age with subacute or acute neuromuscular weakness.
Chou, Shih-Jen; Shieh, Yao-Ching; Yu, Chang-You
2008-07-01
Type C1 botulism outbreaks in Black-faced Spoonbills (Platalea minor) occurred in Taiwan from 2002 to 2003, and hematologic and biochemistry parameters from botulism-paralyzed birds and recovered birds were compared. Values for creatinine and uric acid were higher (P<0.0025) in birds with botulism than in recovered birds. Lower white blood cell counts (P<0.005) and values for alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and triglycerides (P<0.025) were observed in recovered birds. Based on these observations, we suggest that hematologic and biochemistry analyses should be performed to assess the health condition of birds recovering from botulism.
[Sudden death of twins: botulism because of contamination by pap vegetables].
Fischer, D; Freislederer, A; Jorch, G
2004-01-01
Botulism is caused by the blockage of the neural transmission in the cholinergic synapses by botulinum neurotoxin (BoNT) which is produced by Clostridium botulinum or other Clostridia. The classic form of botulism occurs after the ingestion of food contaminated by BoNT. The course of the infection can be asymptomatic, mild with subtle paralysis ("failure to thrive") oder severe with generalized paralysis ("floppy infant"). Infected infants can also die sudden and unexpectedly. These deaths often are attributed to Sudden Infant Death Syndrome (SIDS), unless a thorough postmortem examination reveals Botulism. The rate of fatal Botulism falsely attributed to SIDS is not known, because it is difficult in most cases to show the causal relationship between contamination, disease and death. We report the sudden and unexpected simultaneous death of twins of 22 months which could be attributed to Botulism. Contamination of food, colonization of the gut by Clostridia and infection with specific pathomorphological changes could be proven. The initial suspicion of infanticide could be excluded. lt could be shown, that Botulism is a potential cause of simultaneous unexpected deaths in twins.
[Intoxication of botulinum toxin].
Chudzicka, Aleksandra
2015-09-01
Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. © 2015 MEDPRESS.
Characterizing the fecal microbiota of infants with botulism.
Shirey, T Brian; Dykes, Janet K; Lúquez, Carolina; Maslanka, Susan E; Raphael, Brian H
2015-11-23
Infant botulism is the most prevalent form of botulism in the USA, representing 68.5 % of cases reported from 2001-2012. Infant botulism results when botulinum toxin-producing clostridia (BTPC) colonize the infant gut with concomitant in vivo production of the highly potent botulinum neurotoxin (BoNT). The gut microbiota of infants with botulism is largely uncharacterized; therefore, it remains unclear whether the microbiota profile of these patients are distinct in composition, abundance, or diversity. To address this uncertainty, we employed 16S rRNA gene profiling to characterize the fecal microbiota in 14 stool samples among laboratory-confirmed and non-confirmed infant botulism cases. Seven bacterial phyla were identified among all 14 infant stool samples examined. Compared to samples from non-confirmed cases, the fecal microbiota of infant botulism patients displayed significantly higher Proteobacteria abundance. Of the 20 bacterial families identified, Enterobacteriaceae was significantly more abundant in samples from infants with botulism. Firmicutes abundance and the abundance ratio of Firmicutes/Proteobacteria was significantly lower in samples from infants with botulism. Lactobacillus spp. abundance was notably reduced in 12 of the 14 samples. Clostridium botulinum and Clostridium baratii were identified in low relative abundances in confirmed and non-confirmed samples based on their 16S rRNA gene profiles, although their toxigenicity remained undetermined. No significant differences were observed in the number of operational taxonomic units (OTUs) observed or in fecal microbiota diversity between laboratory-confirmed and non-confirmed samples. Correlations between individual phylum abundances and infant age were variable, and no significant differences were shown in number of OTUs observed or in fecal microbiota diversity between samples delineated by overall mean age. Significant differences in Proteobacteria, Firmicutes, and Enterobacteriaceae abundances were identified in the fecal microbiota of infants with botulism when compared to samples from non-confirmed cases. Fecal microbiota diversity was not significantly altered in infants with botulism, and a limited presence of BTPC was shown. It could not be determined whether the fecal microbiota profiles shown here were comparable prior to patient illness, or whether they were the direct result of infant botulism. The results of this study do, however, provide a detailed and descriptive observation into the infant gut microbiota after intestinal colonization by BTPC.
Gay, C T; Marks, W A; Riley, H D; Bodensteiner, J B; Hamza, M; Noorani, P A; Bobele, G B
1988-04-01
We present the first two known cases of infantile botulism in Oklahoma. The first case was due to type B toxin; the second was due to type A toxin. Both cases demonstrate most of the classic features of what now appears to be the most common form of botulism. Infantile botulism is an underrecognized but reversible cause of hypotonia. In most cases, the prognosis is excellent with institution of appropriate supportive care. The recognition of cranial nerve palsies or a history of constipation should raise the suspicion of infantile botulism. Aminoglycoside antibiotics and other agents that may precipitate or exacerbate neuromuscular blockade should be used with extreme caution in hypotonic infants until the cause of the hypotonia is clearly identified.
Dry mouth as an initial sign of food-borne botulism: a case report and review of the literature.
Manfredi, Maddalena; Scoditti, Umberto; Angelini, Monica; de Giampaulis, Piero; Borrini, Bianca Maria; Macaluso, Guido Maria; Pavesi, Giovanni; Vescovi, Paolo
2011-04-01
Botulism is a rare neuroparalytic disease caused by a potent neurotoxin produced by Clostridium botulinum. There are different clinical types of botulism. Early diagnosis of the condition is essential for effective treatment. We report a case of food-borne botulism in identical twins characterized by severe initial oral involvement and a review of the literature about the condition. Copyright © 2011 Mosby, Inc. All rights reserved.
Böhnel, H; Behrens, S; Loch, P; Lube, K; Gessler, F
2001-10-01
Despite the fact that botulism was described in Germany for the first time by Kerner in 1820, the disease is almost forgotten in this country. Only about 10-20 cases of classical botulism (intoxication) are recorded every year, including 1-2 cases of clinical infant botulism. As we assumed a high incidence of botulism to be connected with cases of sudden infant death (SID), we undertook the research work presented here. From every case of unexpected infant death up to 12 months of age, standardised specimens (blood, liver and intestine) were taken at autopsy. They were tested for the presence of botulinum neurotoxin (BoNT) and/or bacterial forms of Clostridium botulinum with subsequent BoNT neutralisation tests by the international standard mouse bioassay. Age, sex, pathological findings and season were recorded. Over a 5-year period, 75 samples including 57 SID cases were tested. Free toxin was found in nine and bacterial forms were detected in six samples. Toxin neutralisation revealed the definite presence of BoNT/BoNT producing bacteria (mainly type E), whereas another 11 toxin tests were inconclusive. According to international literature, these 15 cases are to be interpreted as infant botulism. the results show a remarkable incidence of infant botulism without any known previous medical history, partly hidden as sudden infant death. We propose to systematically search for botulism in connection with sudden infant death.
Marcus, Nir; Hourvitz, Ariel
2002-05-01
Botulism is caused by a neurotoxin produced from the anaerobic, spore forming bacteria--clostridium botulinum. The disease is usually caused by toxins type A, B and E. Since the disease was first recognized in the beginning of the nineteenth century as food poisoning, different forms of intoxication were described. Infantile botulism, wound botulism, infectious botulism and inadvertent botulism are all clinical syndromes caused by the same toxin. The attempt to use the botulinum toxin as biological warfare agent is well known. Recently the potential terrorist use of botulinum toxin has become a real concern. Botulism is characterized by its classic triad: 1) symmetric descending flaccid paralysis with prominent bulbar palsies 2) afebrile patient 3) clear sensorium. The paralysis usually begins in the cranial nerves where blurred vision, dysarthia and dysphagia are the initial complaints. Diagnosis is based on clinical findings, history of suspicious exposure and supportive ancillary testing to rule out other causes of neurologic dysfunction that mimic botulism such as the Guillain-Barre syndrome, Myasthenia Gravis or cerebrovascular stroke. Laboratory confirmation of suspected cases is usually delayed and treatment should begin before confirmation is completed. The treatment includes supportive care, and the administration of antitoxin which reduces mortality if given early. Since community and emergency room physicians may be the first to treat patients with any type of botulinum intoxication, they must know how to diagnose and treat this rare but potentially lethal disease.
[A case report of infant botulism without a history of honey ingestion].
Morikawa, Y; Shishida, N; Toshima, M; Yoshioka, Y; Nukina, M
1994-02-01
A 66-day-old female with infant botulism is reported. She was admitted to our hospital with respiratory failure. Laboratory examinations detected botulinal toxin type A in her feces. This was the first case with no history of honey ingestion among the 13 cases of infant botulism reported in Japan. It is possible that other cases, in which honey had not been consumed, remain undiagnosed. Further studies may be needed to clarify the factors necessary to cause infant botulism.
Date, Kashmira; Fagan, Ryan; Crossland, Sandra; Maceachern, Dorothy; Pyper, Brian; Bokanyi, Rick; Houze, Yolanda; Andress, Elizabeth; Tauxe, Robert
2011-12-01
Foodborne botulism is a potentially fatal paralytic illness caused by ingestion of neurotoxin produced by the spore-forming bacterium Clostridium botulinum. Historically, home-canned vegetables have been the most common cause of botulism outbreaks in the United States. During 2008 and 2009, the Centers for Disease Control and Prevention (CDC) and state and local health departments in Ohio and Washington State investigated three outbreaks caused by unsafe home canning of vegetables. We analyzed CDC surveillance data for background on food vehicles that caused botulism outbreaks from 1999 to 2008. For the three outbreaks described, patients and their family members were interviewed and foods were collected. Laboratory testing of clinical and food samples was done at the respective state public health laboratories. From 1999 to 2008, 116 outbreaks of foodborne botulism were reported. Of the 48 outbreaks caused by home-prepared foods from the contiguous United States, 38% (18) were from home-canned vegetables. Three outbreaks of Type A botulism occurred in Ohio and Washington in September 2008, January 2009, and June 2009. Home-canned vegetables (green beans, green bean and carrot blend, and asparagus) served at family meals were confirmed as the source of each outbreak. In each instance, home canners did not follow canning instructions, did not use pressure cookers, ignored signs of food spoilage, and were unaware of the risk of botulism from consuming improperly preserved vegetables. Home-canned vegetables remain a leading cause of foodborne botulism. These outbreaks illustrate critical areas of concern in current home canning and food preparation knowledge and practices. Similar gaps were identified in a 2005 national survey of U.S. adults. Botulism prevention efforts should include targeted educational outreach to home canners.
Equine Botulinum Antitoxin for the Treatment of Infant Botulism ▿
Vanella de Cuetos, Elida E.; Fernandez, Rafael A.; Bianco, María I.; Sartori, Omar J.; Piovano, María L.; Lúquez, Carolina; de Jong, Laura I. T.
2011-01-01
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. PMID:21918119
Equine botulinum antitoxin for the treatment of infant botulism.
Vanella de Cuetos, Elida E; Fernandez, Rafael A; Bianco, María I; Sartori, Omar J; Piovano, María L; Lúquez, Carolina; de Jong, Laura I T
2011-11-01
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.
Infant botulism type Ba: first culture-confirmed case in the United Arab Emirates.
Fathalla, Waseem M; Mohammed, Khalid A; Ahmed, Elamin
2008-09-01
We report on a 3-month-old girl with culture-confirmed infant botulism caused by a rare double toxin-producing Clostridium botulinum type Ba. This case was not related to honey-feeding. The clinical course was prolonged, with minimal spontaneous improvement at onset, and a period of fluctuating motor weakness and nasogastric feeding dependence afterward. Neurophysiologic studies produced normal results. Human botulism immune globulin was administered empirically on day 23 of presentation, with rapid full recovery. This case highlights the importance of pursuing diagnoses of infant botulism despite normal results of neurophysiologic testing and no history of honey-feeding. Our case also demonstrates a favorable response to human botulism immune globulin, despite the relatively late treatment.
Botulism toxemia following laparoscopic appendectomy.
Nystrom, Susan C; Wells, Eden V; Pokharna, Hiren S; Johnson, Laura E; Najjar, Mazen A; Mamou, Fatema M; Rudrik, James T; Miller, Corinne E; Boulton, Matthew L
2012-02-15
We describe a case of botulism infection in a patient who had undergone laparoscopic appendectomy, an occurrence not previously described in the literature. This case exemplifies the need for coordination between clinical and public health personnel to ensure the immediate recognition and treatment of suspected botulism cases.
Botulism from chopped garlic: delayed recognition of a major outbreak.
St Louis, M E; Peck, S H; Bowering, D; Morgan, G B; Blatherwick, J; Banerjee, S; Kettyls, G D; Black, W A; Milling, M E; Hauschild, A H
1988-03-01
Diagnosis of botulism in two teenaged sisters in Montreal led to the identification of 36 previously unrecognized cases of type B botulism in persons who had eaten at a restaurant in Vancouver, British Columbia, during the preceding 6 weeks. A case-control study implicated a new vehicle for botulism, commercial chopped garlic in soybean oil (P less than 10(-4)). Relatively mild and slowly progressive illness, dispersion of patients over at least eight provinces and states in three countries, and a previously unsuspected vehicle had contributed to prolonged misdiagnoses, including myasthenia gravis (six patients), psychiatric disorders (four), stroke (three), and others. Ethnic background influenced severity of illness: 60% of Chinese patients but only 4% of others needed mechanical ventilation (P less than 10(-3]. Trypsinization of serum was needed to show toxemia in one patient. Electromyography results with high-frequency repetitive stimulation corroborated the diagnosis of botulism up to 2 months after onset. Although botulism is a life-threatening disease, misdiagnosis may be common and large outbreaks can escape recognition completely.
Brand, C.J.; Windingstad, R.M.; Siegfried, Lynne M.; Duncan, R.M.; Cook, R.M.
1988-01-01
During the summers of 1981 and 1982, studies were conducted at Jamaica Bay Wildlife Refuge, Long Island, New York, to determine whether annual water-level drawdowns used to create shorebird habitat also led to the occurrence of avian botulism (Clostridium botulinum type C). Low levels of morbidity and mortality from avian botulism occurred on the two ponds throughout both summers, but there was no apparent relationship between the occurrence or rates of botulism losses and drawdowns of the ponds. Botulism also occurred throughout both summers on other areas of the refuge. Botulinal toxin was found in fly larvae associated with avian carcasses, including birds that did not die from botulism. Toxin was not found in other samples of aquatic biota in the ponds, although it was demonstrated in a single sample of decomposing sea lettuce (Ulva lactuca) in Jamaica Bay. Aspergillosis (Aspergillus fumigatus) and salmonellosis (Salmonella spp.) were also frequently-diagnosed causes of morbidity and mortality. We believe that botulinal toxin present in carcasses of birds dying from botulism, or produced postmortem in birds dying from other causes, on the two ponds and other areas in Jamaica Bay were a major source of botulinal toxin. Toxin could be ingested by birds through direct scavenging on carcasses, or by consumption of toxic fly larvae associated with carcasses. Diligent carcass pickup at the two ponds is recommended to reduce mortality from avian botulism.
Dembek, Zygmunt F; Smith, Leonard A; Rusnak, Janice M
2007-11-01
Botulism is a neuroparalytic disease caused by neurotoxins produced by the bacteria Clostridium botulinum. Botulinum neurotoxins (BoNTs) are among the most potent naturally occurring toxins and are a category A biological threat agent. The 7 toxin serotypes of BoNTs (serotypes A-G) have different toxicities, act through 3 different intracellular protein targets, and exhibit different durations of effect. Botulism may follow ingestion of food contaminated with BoNT, from toxin production of C botulinum present in the intestine or wounds, or from inhalation of aerosolized toxin. Intoxication classically presents as an acute, symmetrical, descending flaccid paralysis. Early diagnosis is important because antitoxin therapy is most effective when administered early. Confirmatory testing of botulism with BoNT assays or C botulinum cultures is time-consuming, and may be insensitive in the diagnosis of inhalational botulism and in as many as 32% of food-borne botulism cases. Therefore, the decision to initiate botulinum antitoxin therapy is primarily based on symptoms and physical examination findings that are consistent with botulism, with support of epidemiological history and electrophysiological testing. Modern clinical practice and antitoxin treatment has reduced botulism mortality rates from approximately 60% to < or =10%. The pentavalent botulinum toxoid is an investigational product and has been used for more than 45 years in at-risk laboratory workers to protect against toxin serotypes A to E. Due to declining immunogenicity and potency of the pentavalent botulinum toxoid, novel vaccine candidates are being developed.
Botulism in foals less than 6 months of age: 30 cases (1989-2002).
Wilkins, Pamela A; Palmer, Jonathan E
2003-01-01
Botulism has been recognized as a clinical entity in foals since the 1960s. Also known as "Shaker foal" disease, the toxicoinfectious form of botulism affects foals, with the highest incidence in the United States seen in Kentucky and the mid-Atlantic region. The disease is characterized by progressive muscular weakness caused by the action of botulism neurotoxin at cholinergic neuromuscular junctions. Increased number of episodes and duration of recumbency, muscular trembling, and dysphagia are seen in affected foals. Left untreated, the disease can be rapidly fatal, with death occuring secondary to respiratory muscle paralysis within 24 to 72 hours of the onset of clinical signs. Very mildly affected foals can survive with minimal treatment Despite advances made in treatment of these foals, including administration of botulism antitoxin early in the course of the disease, there is still an impression that the disease carries a high mortality rate. The purpose of this study was to evaluate outcome in 30 foals <6 months of age diagnosed with botulism between 1989 and 2002 at the George D. Widener Large Animal Hospital, New Bolton Center. Two foals were euthanized for economic reasons early in the disease course, and I died while being treated. Survival of treated cases was greater than 96%. Approximately 50% of the cases required oxygen therapy, whereas 30% required mechanical ventilation. All foals, excepting 1 mildly affected foal, received botulism antitoxin. Mean duration of hospitalization was 14 days. With appropriate treatment, foals with botulism have a high survival rate.
Chronic Clostridium botulinum infections in farmers.
Rodloff, Arne C; Krüger, Monika
2012-04-01
Although botulism is usually an acute, often lethal disease that is caused by the ingestion of botulinum neurotoxin, there are also recognized forms like infant botulism, wound botulism, or "botulism of undefined origin" that are characterized by the fact that Clostridium botulinum colonizes the host and produces its toxin in the host. Evidence is presented here that a disease in cattle and in human care takers of diseased animals that has evolved over the past two decades, may be a chronic, visceral form of C. botulinum infection. Copyright © 2012 Elsevier Ltd. All rights reserved.
Caya, James G; Agni, Rashmi; Miller, Joan E
2004-06-01
This review article is designed to thoroughly familiarize all health care professionals with the history, classification, epidemiology, clinical characteristics, differential diagnosis, diagnostic evaluation (including laboratory-based testing), treatment, and prognosis of botulism. It is especially targeted toward clinical laboratorians and includes a detailed enumeration of the important clinical laboratory contributions to the diagnosis, treatment, and monitoring of patients with botulism. Finally, the bioterrorism potential for botulism is discussed, with an emphasis on the clinical laboratory ramifications of this possibility. Included medical periodicals and textbooks accessioned from computerized and manual medical literature searches. More than 1000 medical works published from the 1800s through 2003 were retrieved and reviewed in this process. Pertinent data are presented in textual and tabular formats, the latter including 6 tables presenting detailed information regarding the clinical parameters, differential diagnosis, diagnostic studies, laboratory testing, and therapeutic approaches to botulism. Because botulism is such a rare disease, a keen awareness of its manifestations and prompt diagnosis are absolutely crucial for its successful treatment. The bioterrorism potential of botulism adds further urgency to the need for all health care professionals to be familiar with this disease, its proper evaluation, and timely treatment; the need for such urgency clearly includes the clinical laboratory.
[Botulism: Diagnosis and Therapy].
Wendt, Sebastian; Eder, Ines; Wölfel, Roman; Braun, Peggy; Lippmann, Norman; Rodloff, Arne
2017-09-01
Background Botulism is a rare, life-threatening, time-critical neuroparalytic disease that is frequently a subject of differential diagnostic considerations. But there is much uncertainty regarding diagnosis and therapy. Rapid diagnosis, early antitoxin dose, consistent food hygiene and the sensitization of the population can help to reduce incidence, morbidity and mortality. Methods This overview is based on an epidemiological data inquiry (RKI, ECDC, CDC, WHO) and a selective literature research (pubmed till March 2017). Additionally, the German botulism guideline (2012) and own diagnostical experiences were taken into account. Results The incidence of botulinum toxin intoxication induced by ubiquitous spore-forming Clostridium botulinum (main representative) is < 0.01/100 000 EU citizens. Foodborne botulism is a pure intoxication syndrome (most common form) due to improperly prepared or incorrectly stored food. Wound and infant botulism are kinds of "toxico-infections". A "bulbar" neuroparalysis is a main symptom progressing to a flaccid tetraparesis up to respiratory paralysis. Infant botulism is presented non-specific and is treated only symptomatically; but a special human-derived antitoxin is available at international pharmacies. In case of suspected foodborne or wound botulism antitoxin must be administered as soon as possible, which may also be effective 24 hours after symptoms onset. There is no evidence for adjuvant treatment except of intensive care unit (ICU) therapy. Conclusion Despite typical symptomatology botulism is often diagnosed too late. Early antitoxin administration and ICU therapy are crucial for survival. A consultant laboratory should be contacted for advice. © Georg Thieme Verlag KG Stuttgart · New York.
Botulism Type E Outbreak Associated with Eating a Beached Whale, Alaska
Sobel, Jeremy; Lynn, Tracey; Funk, Elizabeth; Middaugh, John P.
2004-01-01
We report an outbreak of botulism that occurred in July 2002 in a group of 12 Alaskan Yu'pik Eskimos who ate blubber and skin from a beached beluga whale. Botulism death rates among Alaska Natives have declined in the last 20 years, yet incidence has increased. PMID:15498179
Early diagnosis and treatment in a child with foodborne botulism.
Proverbio, Maria Renata; Lamba, Marta; Rossi, Alessandro; Siani, Paolo
2016-06-01
Foodborne botulism is a neuroparalytic disease caused by ingestion of food contaminated with botulinum toxins. Despite rare the mortality rate is high if untreated. Diagnosis of botulism is still a challenge for clinician, due to the variability of clinical manifestations and disease course. We report on a child with type B botulin intoxication who was early diagnosed and treated underlining that clinical suspicion is crucial to start prompt treatment. An 11-year-old boy presented with bilateral ptosis and mydriasis, dry mouth, difficulty in swallowing, dysphonia, urine retention and constipation. Clear sensorium and no fever were observed. Immediately the suspicion of botulism was risen and botulinum antitoxin was administered. 3 days later serum and rectal samples tested positive for Clostridium botulinum. The patient completely recovered when discharged from hospital. Foodborne botulism is still possible in developed countries. The confirmation test of botulism requires some days. To avoid long delays between intoxication and diagnosis prompt clinical suspicion is thus crucial. The outcome depends on rapid implementation of appropriate management with intensive respiratory care and antitoxin administration. Copyright © 2015 Elsevier Ltd. All rights reserved.
Livers provide a reliable matrix for real-time PCR confirmation of avian botulism.
Le Maréchal, Caroline; Ballan, Valentine; Rouxel, Sandra; Bayon-Auboyer, Marie-Hélène; Baudouard, Marie-Agnès; Morvan, Hervé; Houard, Emmanuelle; Poëzevara, Typhaine; Souillard, Rozenn; Woudstra, Cédric; Le Bouquin, Sophie; Fach, Patrick; Chemaly, Marianne
2016-04-01
Diagnosis of avian botulism is based on clinical symptoms, which are indicative but not specific. Laboratory investigations are therefore required to confirm clinical suspicions and establish a definitive diagnosis. Real-time PCR methods have recently been developed for the detection of Clostridium botulinum group III producing type C, D, C/D or D/C toxins. However, no study has been conducted to determine which types of matrices should be analyzed for laboratory confirmation using this approach. This study reports on the comparison of different matrices (pooled intestinal contents, livers, spleens and cloacal swabs) for PCR detection of C. botulinum. Between 2013 and 2015, 63 avian botulism suspicions were tested and 37 were confirmed as botulism. Analysis of livers using real-time PCR after enrichment led to the confirmation of 97% of the botulism outbreaks. Using the same method, spleens led to the confirmation of 90% of botulism outbreaks, cloacal swabs of 93% and pooled intestinal contents of 46%. Liver appears to be the most reliable type of matrix for laboratory confirmation using real-time PCR analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.
Investigation of serology for diagnosis of outbreaks of botulism in cattle.
Mawhinney, I; Palmer, D; Gessler, F; Cranwell, M; Foyle, L; Otter, A; Payne, J; Strugnell, B
2012-06-01
Serology has been used to diagnose retrospectively types C and D outbreaks of botulism in cattle in Australia and this study has investigated whether the approach would be applicable in England and Wales. Three hundred sera from routine surveillance submissions in England and Wales were used as a negative control population. Some stored sera were available from a small number of clinical cases of botulism and 125 samples were collected from cohort groups of clinical cases in four new outbreaks of botulism. Three of these outbreaks were identified as being caused by type D Clostridium botulinum toxin. Sera were tested by antibody ELISA in laboratories in Australia and Germany. There was no increase in the proportion of animals seropositive to type C or D antibody in the botulism-associated cattle. The proportion of samples which were seropositive to type D antibodies was <2% in both the negative control and outbreak populations. It was concluded that single time serology is unlikely to be helpful for retrospective diagnosis of outbreaks of type D botulism in England and Wales. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
[Type B botulism: a family outbreak].
Lamboley, G; Mandel, R; Müller, S; Douard, P; Métral, S; Durand, P
2001-03-01
Three cases of an outbreak of familial foodborne botulism are reported. The food incriminated could not be identified despite a careful investigation into the food history of the patients. The outcome was good following endotracheal ventilation and botulism antitoxin trivalent therapy. In France, foodborne botulism is an uncommon public health disease, and with a good prognosis when the diagnosis is promptly performed. The value of emergency electromyographic findings is emphasized, particularly when the repetitive stimulation of the motor nerve shows a presynaptic block of neuromuscular transmission. Management depends on the symptomatology, and trivalent antitoxin therapy is the only specific treatment.
Cases of type C botulism in broiler chickens.
Dohms, J E; Allen, P H; Rosenberger, J K
1982-01-01
Twenty-seven cases of type C botulism were studied in integrated broiler operations on the Delmarva Peninsula. Single and repeated outbreaks in broiler flocks were observed. No botulinum toxin was found in litter and feed samples despite repeated testing. Clostridium botulinum type C was cultured from litter, feed, and tissues of morbid and clinically normal chickens sampled from farms in which flocks experienced botulism. Clostridium botulinum type C could not be cultured from tissues of clinically normal chickens taken from a farm without a flock history of botulism or from caged broilers reared in semi-isolation.
Caya, J G
2001-01-01
The anaerobic bacterium Clostridium botulinum causes disease by elaborating an extremely potent neurotoxin that inhibits release of acetylcholine at presynaptic nerve endings, thereby resulting in a descending flaccid paralysis and autonomic nervous system dysfunction. Possible ophthalmological effects of this neurotoxin are many and typically constitute the earliest manifestations of botulism. This review summarizes the medical literature on botulism with regard to historical perspective, epidemiology, clinical manifestations, and treatment. Ophthalmological findings of botulism are tabulated and their frequencies are provided. Finally, the bioterrorism/biologic warfare ramifications of botulinum toxin are briefly discussed.
Rocke, T.E.; Friend, M.
1999-01-01
Avian botulism is a paralytic, often fatal, disease of birds that results when they ingest toxin produced by the bacterium, Clostridium botulinum. Seven distinct types of toxin designated by the letters A to G have been identified (Table 38.1). Waterfowl die-offs due to botulism are usually caused by type C toxin; sporadic die-offs among fish-eating birds, such as common loons and gulls, have been caused by type E toxin. Type A botulinum toxin has also caused disease in birds, most frequently in domestic chickens. Types B, D, F, and G are not known to cause avian botulism in North America.
Occurrence of avian botulism in Korea during the period from June to September 2012.
Jang, Il; Kang, Min-Su; Kim, Hye-Ryoung; Oh, Jae-Young; Lee, Jae-Il; Lee, Hee-Soo; Kwon, Yong-Kuk
2014-12-01
Botulism is a paralytic disease caused by the botulinum neurotoxin produced by Clostridium botulinum. In the summer season in Korea, intensive outbreaks of avian botulism were reported in both poultry and wild birds, including five Korean native chicken farms (HanHyup NO.3), one pheasant (Phasianus colchicus karpowi) farm, and one community of spot-billed ducks (Anas poecilorhyncha). The affected domestic birds showed 24.5% to 58.3% mortality, with specific clinical signs including ataxia, limber neck, and diarrhea. To confirm the botulinum toxin, neutralization tests were performed on sera (four Korean native chicken farms and one pheasant farm) or culture supernatant (spot-billed ducks). Additionally, the contents of the cecum and liver from poultry presenting signs suggestive of botulism were inoculated to isolate the pathogen. The toxin genes were then detected by polymerase chain reaction (PCR). Through the neutralization tests, it was possible to diagnose the botulism and, except in the case of one Korean native chicken farm, to identify the type of pathogen. Using detection by PCR, except in two cases of the Korean native chicken farms, the botulinum toxin gene was found. Additionally, in four cases, it was possible to identify the C/D mosaic type using PCR. This paper reports the first occurrence of avian botulism in domestic birds and the first detection of botulism caused by this mosaic type in Korea.
Brain acetycholinesterase activity in botulism-intoxicated mallards
Rocke, T.E.; Samuel, M.D.
1991-01-01
Brain acetylcholinesterase (AChE) activity in captive-reared mallards (Anas platyrhynchos) that died of botulism was compared with euthanized controls. AChE levels for both groups were within the range reported for normal mallards, and there was no significant difference in mean AChE activity between birds that ingested botulism toxin and died and those that did not.
Takotsubo-like Myocardial Dysfunction in a Patient with Botulism.
Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki
2017-11-01
Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease.
Takotsubo-like Myocardial Dysfunction in a Patient with Botulism
Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki
2017-01-01
Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease. PMID:28924131
Avian botulism: geographic expansion of a historic disease
Locke, Louis N.; Friend, Milton
1989-01-01
Avian botulism is a paralytic, often fatal disease of birds resulting from ingestion of toxin produced by the bacterium Clostridium botulinum. Waterfowl die-offs from the botulism are usually caused by type C toxin; sporadic die-offs among fish-eating birds, such as common loons (Gavia immer) and gulls, have been caused by type E toxin.
Anza, I.; Vidal, D.; Feliu, J.; Crespo, E.
2016-01-01
ABSTRACT Avian botulism kills thousands of waterbirds every year, including endangered species, but information about the differences between species in vulnerability to botulism outbreaks and the capacity to act as carriers of Clostridium botulinum is still poorly known. Here, we estimated the vulnerability to botulism of 11 waterbird species from Mediterranean wetlands by comparing the number of affected birds with the census of individuals at risk. The capacity of different species to act as carriers was studied by detecting the presence of the C. botulinum type C/D botulinum neurotoxin (BoNT) gene in fecal samples and prey items of waterbirds in the wild and by the serial sampling of cloacal swabs of birds affected by botulism. We found differences among species in their vulnerabilities to botulism, probably related to feeding habits, season of arrival, turnover, and, possibly, phylogenetic resilience. The globally endangered white-headed duck (Oxyura leucocephala) showed mortality rates in the studied outbreaks of 7% and 17% of the maximum census, which highlights botulism as a risk factor for the conservation of the species. Invasive water snails, such as Physa acuta, may be important drivers in botulism epidemiology, because 30% of samples tested positive for the BoNT gene during outbreaks. Finally, our results show that birds may excrete the pathogen for up to 7 days, and some individuals can do it for longer periods. Rails and ducks excreted C. botulinum more often and for longer times than gulls, which could be related to their digestive physiology (i.e., cecum development). IMPORTANCE Botulism is an important cause of mortality in waterbirds, including some endangered species. The global climate change may have consequences in the ecology of wetlands that favor the occurrence of botulism outbreaks. Here, we offer some information to understand the ecology of this disease that can be useful to cope with these global changes in the future. We have found that some species (i.e., coots and dabbling ducks) are more vulnerable to botulism and have a more relevant role in the onset and amplification of the outbreaks than other species (i.e., flamingos and grebes). Feeding habits can explain these differences in part; in addition to the well-known role of necrophagous fly maggots, we found here that water snails are frequent carriers of Clostridium botulinum. This is relevant, because these water snails can thrive in eutrophic and polluted wetlands, exacerbating other changes driven by climate change in wetlands. PMID:27016572
Medical treatment for botulism.
Chalk, Colin; Benstead, Tim J; Keezer, Mark
2011-03-16
Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear. To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism. We searched the Cochrane Neuromuscular Disease Group Specialized Register (10 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (10 January 2010 in The Cochrane Library, Issue 4 2010), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011). We reviewed bibliographies, and contacted authors and experts. We included randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine. Two authors selected studies, assessed risk of bias and extracted data independently onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events. A single randomized controlled trial met the inclusion criteria. This trial evaluated human-derived botulinum immune globulin for the treatment of infant botulism. This study included 59 treatment patients and 63 control patients. There were no deaths in either group making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on duration of hospitalization (mean difference (MD) 3.10 weeks, 95% confidence interval (CI) 1.68 to 4.52), mechanical ventilation (MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (relative risk reduction 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11). There is good evidence supporting the use of human-derived botulinum immune globulin in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding among treated patients. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.
Anza, I; Vidal, D; Feliu, J; Crespo, E; Mateo, R
2016-05-15
Avian botulism kills thousands of waterbirds every year, including endangered species, but information about the differences between species in vulnerability to botulism outbreaks and the capacity to act as carriers of Clostridium botulinum is still poorly known. Here, we estimated the vulnerability to botulism of 11 waterbird species from Mediterranean wetlands by comparing the number of affected birds with the census of individuals at risk. The capacity of different species to act as carriers was studied by detecting the presence of the C. botulinum type C/D botulinum neurotoxin (BoNT) gene in fecal samples and prey items of waterbirds in the wild and by the serial sampling of cloacal swabs of birds affected by botulism. We found differences among species in their vulnerabilities to botulism, probably related to feeding habits, season of arrival, turnover, and, possibly, phylogenetic resilience. The globally endangered white-headed duck (Oxyura leucocephala) showed mortality rates in the studied outbreaks of 7% and 17% of the maximum census, which highlights botulism as a risk factor for the conservation of the species. Invasive water snails, such as Physa acuta, may be important drivers in botulism epidemiology, because 30% of samples tested positive for the BoNT gene during outbreaks. Finally, our results show that birds may excrete the pathogen for up to 7 days, and some individuals can do it for longer periods. Rails and ducks excreted C. botulinum more often and for longer times than gulls, which could be related to their digestive physiology (i.e., cecum development). Botulism is an important cause of mortality in waterbirds, including some endangered species. The global climate change may have consequences in the ecology of wetlands that favor the occurrence of botulism outbreaks. Here, we offer some information to understand the ecology of this disease that can be useful to cope with these global changes in the future. We have found that some species (i.e., coots and dabbling ducks) are more vulnerable to botulism and have a more relevant role in the onset and amplification of the outbreaks than other species (i.e., flamingos and grebes). Feeding habits can explain these differences in part; in addition to the well-known role of necrophagous fly maggots, we found here that water snails are frequent carriers of Clostridium botulinum This is relevant, because these water snails can thrive in eutrophic and polluted wetlands, exacerbating other changes driven by climate change in wetlands. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
[Clinical analysis of three cases with infant botulism and review of literature].
Zhang, Jie; Xu, Wenrui; Zhao, Manman; Wu, Ye; Zhang, Xin; Zhang, Chunyu; Wang, Ying; Liu, Xueqin; Lu, Shan; Xu, Xuefang
2016-03-01
To analyze the clinical characteristics and diagnosis of three cases with infant botulism. Clinical data of three clinically diagnosed cases with infant botulism in May 2015 in Peking University First Hospital were retrospectively analyzed. Literature search at databases of PubMed, Wanfang, China National Knowledge Infrastructure and VIP with the key words"infant AND botulism". The date of literature retrieval was from the database founding to November 2015. The characteristics of infant botulism were summarized through review of literature. Three patients were infants of 4-8 months of age, and all had acute onsets of anorexia and poor response. All of them had normal psychomotor development previously, and without clear history of exposure to poisons. The main findings on physical examination were reduced muscle strength and hypotonia, dullness or disappeared pupillary light reflex, reduced facial expression, weak crying and dysphagia. Unexpectedly their states of consciousness were relatively normal. Finally, through identification and PCR genotyping of bacteria in stool, 2 cases were confirmed as Clostridium (C.) botulinum type B infection. Totally 446 reports were retrieved from foreign language literature and 52 reports from Chinese literature. More than 3,000 cases of infant botulism cases were reported in the world. Rare cases were reported in China and only 1 case was reported in 2000. Most cases of infant botulism had no clear exposure history. The main clinical manifestations are hypotonia, cranial nerve paralysis, flaccid paralysis, but different patients may have different presentations. Detection of C. Botulinum and its toxin in stool can help to confirm the diagnosis. Infant botulism is relatively rare in China, which may be related to the insufficient understanding and inspection level of the disease. It might be underestimated in China.
AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine.
Maselli, R A; Bakshi, N
2000-07-01
Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive. Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific. In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data. Copyright 2000 American Association of Electrodiagnostic Medicine.
Fagan, Ryan P; Neil, Karen P; Sasich, Randy; Luquez, Carolina; Asaad, Hakam; Maslanka, Susan; Khalil, Wajahat
2011-11-01
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.
Cranial Neuropathies and Neuromuscular Weakness: A Case of Mistaken Identity
Adams, Daniel Z.; King, Andrew; Kaide, Colin
2017-01-01
We describe a case of wound botulism initially thought to represent Miller-Fisher variant Guillain-Barré syndrome (MFS). Botulism classically presents with the so-called “four D’s” (diplopia, dysarthria, dysphagia, dry mouth) with symmetric, descending weakness. MFS presents with a triad of limb-ataxia, areflexia, and ophthalmoplegia, with variable cranial nerve and extremity involvement. The distinction can be difficult but is important as early initiation of botulinum antitoxin is associated with improved patient outcomes in cases of botulism. Furthermore, it is important to recognize intravenous drug use as a risk factor in the development of botulism, especially given an increase in injection drug use. PMID:29849352
Cranial Neuropathies and Neuromuscular Weakness: A Case of Mistaken Identity.
Adams, Daniel Z; King, Andrew; Kaide, Colin
2017-08-01
We describe a case of wound botulism initially thought to represent Miller-Fisher variant Guillain-Barré syndrome (MFS). Botulism classically presents with the so-called "four D's" (diplopia, dysarthria, dysphagia, dry mouth) with symmetric, descending weakness. MFS presents with a triad of limb-ataxia, areflexia, and ophthalmoplegia, with variable cranial nerve and extremity involvement. The distinction can be difficult but is important as early initiation of botulinum antitoxin is associated with improved patient outcomes in cases of botulism. Furthermore, it is important to recognize intravenous drug use as a risk factor in the development of botulism, especially given an increase in injection drug use.
Infant botulism in Costa Rica: first report from Central America.
Hernández-de Mezerville, Marcela; Rojas-Solano, Mariela; Gutierrez-Mata, Alfonso; Hernández-Con, Laura; Ulloa-Gutierrez, Rolando
2014-01-15
Clostridium botulinum is known to cause descending paralysis in infants throughout the world. The subject of this study was a three-month-old Costa Rican boy who was hospitalized because of poor suction and feeding, hypotonia, and constipation. Clinical history and physical examination findings suggested infant botulism. Samples were sent to the Winnipeg Public Health Laboratory, where Clostridium botulinum toxin A was identified by PCR and culture from the stools, making this the first report of infant botulism in Central America. Although infant botulism is a known disease, the limitations in identifying it in Central America contributes to the misdiagnosis and under-reporting of this disease.
Type F botulism due to neurotoxigenic Clostridium baratii from an unknown source in an adult.
McCroskey, L M; Hatheway, C L; Woodruff, B A; Greenberg, J A; Jurgenson, P
1991-11-01
Type F botulism was confirmed in a 54-year-old male with signs compatible with botulism who reported to the emergency unit of a hospital. Botulinal neurotoxin was detected in the patient's serum and fecal specimens, and a neurotoxigenic organism whose physiologic characteristics correspond to those of Clostridium baratii was isolated. The toxin produced by the isolate was neutralized by type F botulinal antitoxin and cross-neutralized with lower efficiency by type E antitoxin. The patient's food history was not suggestive of botulism, and it seems likely that the illness was due to colonization of the gut.
Type F botulism due to neurotoxigenic Clostridium baratii from an unknown source in an adult.
McCroskey, L M; Hatheway, C L; Woodruff, B A; Greenberg, J A; Jurgenson, P
1991-01-01
Type F botulism was confirmed in a 54-year-old male with signs compatible with botulism who reported to the emergency unit of a hospital. Botulinal neurotoxin was detected in the patient's serum and fecal specimens, and a neurotoxigenic organism whose physiologic characteristics correspond to those of Clostridium baratii was isolated. The toxin produced by the isolate was neutralized by type F botulinal antitoxin and cross-neutralized with lower efficiency by type E antitoxin. The patient's food history was not suggestive of botulism, and it seems likely that the illness was due to colonization of the gut. PMID:1774272
Infant botulism: clinical spectrum and epidemiology.
Thompson, J A; Glasgow, L A; Warpinski, J R; Olson, C
1980-12-01
Between 1977 and 1979, 12 cases of infant botulism were diagnosed in Utah, and 87 control patients (normal, nonbotulism neurologic disease, and nonbotulism systemic disease) were evaluated. Observations from these patients suggest an expanded clinical spectrum of infant botulism including asymptomatic carriers of organism; mild hypotonia and failure to thrive; typical cases with constipation, bulbar weakness, and hypotonia; and children with a picture compatible with sudden infant death syndrome. Clostridium botulinum was isolated from the stools of three normal control infants and nine control infants who had neurologic diseases that were clearly not infant botulism. These infants were termed "asymptomatic carriers" of the organism. The occurrence of the asymptomatic carrier state suggests that a diagnosis of infant botulism cannot be made on a basis of culture results alone, but must rest in historical documentation and physical confirmation of progressive bulbar and extremity weakness with ultimate complete resolution of symptoms and findings over a period of several months. A common set of environmental features characterizes the home environment of children with infant botulism and "asymptomatic carriers" and includes: nearby constructional or agricultural soil disruption, dusty and windy conditions, a high water table, and alkaline soil conditions.
[Two horses with neurological symptoms: could this be equine botulism?].
Roest, H I J; de Bruijn, C M; Picavet, M T J E; Prins, B; Parmentier, D; de Zwart, G M A M; Dijkstra, Y E; van Zijderveld, F G
2009-10-01
Symptoms, diagnosis and therapy of equine botulism are discussed by the presentation of two detailed reports of horses with neurological symptoms and the results of laboratory investigations over the period 2003-2008 in the Netherlands. In addition a brief summary of the available literature is presented. Prevailing symptoms of botulism in horses include paralysis of the tongue, salvation, dysphagia and paresis and paralysis of the skeletal muscles, as well as signs of colic. Symptoms and prognosis vary with the amount of botulinum neurotoxin (BoNT) involved. For early clinical diagnosis of botulism thorough investigation of the facial nerves is important, for instance by the use of the 'Tongue Stress Test'. Laboratory results often remain negative, probably due to the sampling time, the high sensitivity of horses for botulinum neurotoxin or treatment with antitoxins. Most clinical cases in horses are caused by botulinum neurotoxin B (BoNT/B). For therapy to be successful antiserum needs to be administered in the earliest possible stage of the disease and this should be supported by symptomatic therapy. Botulism is a feed-related intoxication caused by either carcasses in the roughage or BoNT/B production after poor conservation of grass silage. This is the main source of botulism in horses due to the popularity of individually packed grass silage as feed for horses. As long as no vaccine is available in the Netherlands quality control of silage and haylage is strictly recommended in order to reduce the risk of botulism in horses.
Infantile botulism: a case report and review.
Brown, Nicole; Desai, Sameer
2013-12-01
Infantile botulism is the result of ingestion of Clostridium botulinum spores, and is the most common form of infection with botulism in the United States. Ninety percent of cases occur in infants <6 months old. The infants typically present with vague symptoms such as hypotonia and poor feeding. This article reports an infant with confirmed infantile botulism that presented to the Emergency Department (ED) with complaints of decreased feeding and absence of bowel movements for >1 week. Review a case of infantile botulism, its diagnosis, and treatment. A 4-month-old healthy Caucasian male presented to the ED with a 6-day history of decreased feeding after referral from the pediatrician. He had not had a bowel movement for 9 days, and his parents were also concerned about increasing weakness, as he was no longer able to hold his head up on his own. In the ED, he was minimally interactive. His vital signs were within normal limits, and he had hypoactive bowel sounds and decreased tone throughout. He was admitted to the Children's Hospital and eventually transferred to the Pediatric Intensive Care Unit requiring intubation and mechanical ventilation. The botulism immunoglobulin was administered, and a diagnosis was confirmed with positive botulinum toxin in the stool samples. Full recovery was made by the infant. Awareness of the symptoms of botulism and a high degree of clinical suspicion is needed to make a prompt diagnosis. Copyright © 2013 Elsevier Inc. All rights reserved.
Small Molecules Showing Significant Protection of Mice against Botulinum Neurotoxin Serotype A
2010-04-13
Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism that could afflict large, unprotected...that is effective for treating infant botulism at a cost of US $45,300 per treatment regimen. Antibodies can neutralize the extracellular but not the...Inhibitors, Therapeutics, Antidotes, Countermeasures, Botulism , Botulinum Neurotoxins, In Vivo Study, and Mouse Protection. Yuan-Ping Pang, Jon Davis
Type E botulism outbreaks: a manual for beach managers and the public
2012-01-01
The Great Lakes basin has undergone a resurgence of Type E botulism (often referred to as avian botulism) in recent years, characterized by dead birds and fish along the shores of the Great Lakes. The number of deaths and areas affected appear to be increasing to levels that induce concern about the ecological health of the Great Lakes nearshore waters.
Avian botulism E=epizootiology on sewage oxidation ponds in Utah
Moulton, Daniel W.; Jensen, Wayne I.; Stewart, Sondra K.
1976-01-01
In the microenvironment concept of avian botulism epizootiology, it is hypothesized that invertebrate carcasses may serve both as a substrate for toxin production by Clostridium botulinum type C and as a vehicle for toxin transmission to water birds. We field-tested that hypothesis by attempting to induce botulism in wing-clipped mallard ducks (Anas platyrhynchos) on sewage oxidation ponds in Utah. The experimental ponds were inoculated with C. botulinum spores in June 1974. Aquatic insect populations were monitored throughout the summer. Rotenone was used in August to kill insects in two ponds (one served as control), thereby providing potential substrate for clostridial growth and toxin production. Botulism was not detected among the birds even though they routinely ingested invertebrate carcasses. Samples of dead invertebrates contained no botulinum toxin. We concluded that the microenvironment concept, as it now stands, cannot always be a sufficient explanation of how type C botulism epizootics are initiated in nature. Other microbes may inhibit the growth of clostridial cells or destroy botulinum toxin.
Infant botulism: is there an association with thiamine deficiency?
Ringe, Hannelore; Schuelke, Markus; Weber, Sven; Dorner, Brigitte G; Kirchner, Sebastian; Dorner, Martin B
2014-11-01
Infant botulism is an acute life-threatening condition and diagnosis is frequently delayed. Therefore, the best time window to administer specific antibodies, at present the only etiology-based therapy, is often missed, entailing long periods of hospitalization in the PICU. Here we present a 3-month-old boy with infant botulism and respiratory failure, who quickly and favorably responded to thiamine supplementation. From the feces we isolated Clostridium botulinum serotype A2. In addition to producing botulinum neurotoxin A, this strain carried the thiaminase I gene and produced thiaminase I. Accordingly, the child's feces were positive for thiaminase I activity. Because C botulinum group I strains are capable of producing thiaminase I, we speculate that thiamine degradation might further aggravate the paralytic symptoms caused by botulinum neurotoxins in infant botulism. Thus, supportive supplementation with thiamine could be beneficial to speed up recovery and to shorten hospitalization in some patients with infant botulism. Copyright © 2014 by the American Academy of Pediatrics.
A childhood-onset intestinal toxemia botulism during chemotherapy for relapsed acute leukemia.
Ohyama, Noriko; Torio, Michiko; Nakashima, Kentaro; Koga, Yuuki; Kanno, Shunsuke; Nishio, Hisanori; Nishiyama, Kei; Sasazuki, Momoko; Kato, Haru; Asakura, Hiroshi; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Sakai, Yasunari; Ohga, Shouichi
2017-09-18
Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.
Outbreak of type A foodborne botulism at a boarding school, Uganda, 2008.
Viray, M A; Wamala, J; Fagan, R; Luquez, C; Maslanka, S; Downing, R; Biggerstaff, M; Malimbo, M; Kirenga, J B; Nakibuuka, J; Ddumba, E; Mbabazi, W; Swerdlow, D L
2014-11-01
Botulism has rarely been reported in Africa. In October 2008, botulism was reported in three Ugandan boarding-school students. All were hospitalized and one died. A cohort study was performed to assess food exposures among students, and clinical specimens and available food samples were tested for botulinum toxin. Three case-patients were identified; a homemade, oil-based condiment was eaten by all three. In the cohort study, no foods were significantly associated with illness. Botulinum toxin type A was confirmed in clinical samples. This is the first confirmed outbreak of foodborne botulism in Uganda. A homemade, oil-based condiment was the probable source. Consumption of homemade oil-based condiments is widespread in Ugandan schools, putting children at risk. Clinicians and public health authorities in Uganda should consider botulism when clusters of acute flaccid paralysis are seen. Additionally, schools should be warned of the hazard of homemade oil-based condiments, and take steps to prevent their use.
[Botulism an a 38-year-old man after ingestion of garlic in chilli oil].
Lohse, Nicolai; Kraghede, Poul G; Mølbak, Kåre
2003-07-21
Botulism is a rare but potentially fatal disease caused by toxins produced by Clostridium botulinum. We report a case of botulism in a 38-year-old man after eating canned "garlic in chilli-oil". The patient was treated with antiserum. The diagnosis was confirmed by detection of botulinum B toxin by a bio-assay and growth of Clostridium botulinum from the food left-overs.
Anza, Ibone; Vidal, Dolors; Mateo, Rafael
2014-12-01
Avian botulism outbreaks spread through the bird carcass-maggot cycle, in which Clostridium botulinum and blowflies interact to ensure their reproduction in a mutualistic relationship where neurotoxin/spore-bearing maggot is one of the keystones. Here we investigated the hypothesis that adult blowflies may also play a significant role in botulism outbreaks by carrying C. botulinum cells between carcasses. We carried out a field experiment placing bird carcasses free of C. botulinum type C/D in containers only accessible to necrophagous flying insects in wetlands where avian botulism outbreaks were occurring and in control sites. Additionally, we performed laboratory trials to evaluate if blowflies may carry C. botulinum type C/D and for how long. Maggots bearing C. botulinum type C/D developed in 27.5% of carcasses placed in wetlands during botulism outbreaks. Calliphoridae flies in laboratory trials were able to transfer C. botulinum between two points and excreted it in their spots for up to 24 h after an infective feeding. Our results confirm that adult necrophagous flies play a role in the spreading of botulism outbreaks, which have implications in the epidemiology of this disease. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.
What not to say: risk communication for botulism.
Glik, Deborah C; Drury, Allison; Cavanaugh, Clint; Shoaf, Kimberley
2008-03-01
This formative research study used qualitative methods to test the suitability of messages about botulism for the general public. Nine focus group interviews and 27 cognitive interviews were conducted with diverse audiences to pretest radio, television, and fact sheet messages predicated on a hypothetical terrorist attack using botulinum toxin. Narrative data were collected, transcribed, coded, and analyzed using content domains based on risk and health communication theories. While participants accepted the need for materials, the messages produced contained images and references describing botulism as a toxin-caused illness spread both by food and water contamination as well as by airborne means. The audience's lack of understanding of the term toxin and an imperfect understanding of airborne transmission of a toxic substance meant that some people interpreted botulism as being an infectious disease rather than a type of poisoning. The communication materials did not clearly show how the set of botulism symptoms are unique and described the anti-toxin as "not a cure," thus compounding the audience's misunderstanding. Using models from cognitive and developmental psychology, our findings were interpreted to show that certain terms evoke or elicit long-held conceptual frameworks that lay audiences use to explain medical phenomena. Relevant to botulism, poisoning events are distinct from infectious diseases, but prepared messages did not reinforce these distinctions. Ignoring how people organize preexisting health information when trying to communicate new information is a prescription for failure, especially in a crisis risk communication scenario. Findings from this study have been used by the Centers for Disease Control and Prevention to reformulate pre-event crisis risk communication materials for botulism.
Barash, Jason R.; Arnon, Stephen S.
2004-01-01
A retrospective study of Clostridium botulinum strains isolated from patients from California with infant botulism identified the fourth known C. botulinum strain that produces both type B and type F botulinum toxins. This unique strain represented 0.12% of the California infant botulism case isolates from 1976 to 2003. The relative concentrations of type B and F toxins produced were temperature dependent. PMID:15071029
Friend, Milton; Locke, Louis N.; Kennelly, James J.
1985-01-01
What is avian botulism? Avian botulism, or Western duck sickness, is one of the three most important disease problems of wild migratory birds. Each year, many birds are paralyzed or die after exposure to a toxin produced by the botulinum bacterium. Two of the seven toxin types that have been identifies cause mortality in wild birds; one of these types, type C, is most often associated with dieoffs of ducks, while type E primarily affects gulls and loons.
Infant botulism: first two confirmed cases in Slovenia and literature review.
Radšel, Anja; Andlovic, Alenka; Neubauer, David; Osredkar, Damjan
2013-11-01
In Europe, infant botulism is a rare but probably under-diagnosed disease. With the intent to spread the awareness of this potentially life-threatening disease, we present a review of the literature with the emphasis on European epidemiology and a practical approach to diagnosis. We also report the first two confirmed cases of infant botulism in Slovenia and describe our way to the final diagnosis in a clinical setting where all appropriate diagnostic tests and treatment options are not readily available. The second case is particularly interesting, presenting with profound diarrhea following initial constipation, an unlikely symptom for an infant with botulism and possibly caused by Bacteroides fragilis. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
[Infant botulism: case report and review].
Arriagada S, Daniela; Wilhelm B, Jan; Donoso F, Alejandro
2009-04-01
Botulism is a rare disease in Chile and of the known clinical presentation, infant botulism is the most common. We report the case of a previously healthy seven month old male infant with a two weeks history of rinorrea, cough, fatigue, constipation and progressive weakness after the consumption of honey. Stool cultures were positive for Clostridium botulinum group 1 type A and electromyography was compatible with the diagnosis. The patient evolved with arterial hypertension, interpreted as secondary to autonomic dysfunction, which responded to calcium channel blockers. Muscle tone improved progressively during the following four weeks. Infant botulism is a potentially fatal disease; diagnosis can be difficult given the broad clinical manifestations. Prevention should focus on education of parents of infants as well as medical personnel.
Kazanjian, Powel
2018-04-17
In 1919, three deadly outbreaks of botulism caused by consumption of canned olives packed in California captured national headlines. In all of the outbreaks, which occurred in separate locales, unsuspecting people died after consuming tainted food during a banquet or family meal. The press's sensational portrayal of canned food as hazardous aroused alarm among consumers at a time when commercial canning was becoming more common. Intent on restoring the image of their product as safe and wholesome, canning industry leaders funded a "botulism commission" of scientific experts in 1919 to investigate how to systematically eliminate the threat of botulism that had imperiled their business. The commissioners identified the scientific reasons for the outbreaks, and on the basis of their findings, the California Department of Public Health issued explicit recommendations for sterilization procedures intended to ensure safety. However, the department did not mandate inspections for all canneries. When commercially packed fruits and vegetables continued to cause botulism, industry leaders voluntarily backed a cannery inspection act to legally require all California canners to possess appropriate equipment and follow scientifically validated sterilization procedures. After the California legislature approved the act in 1925, canneries were inspected, regulations were enforced, and no further outbreaks occurred. This botulism epidemic is an example of a disease outbreak that was controlled when business interests became aligned with public health goals. The press's portrayal of afflicted persons as innocent victims and worthy citizens galvanized businessmen to implement safeguards to protect consumers from botulism intoxication. To preserve their customer base and salvage their corporations, leaders of the canning industry acknowledged the public health threat of their unregulated procedures and acted on the recommendations of scientists.
Infant botulism following honey ingestion
Abdulla, C O; Ayubi, A; Zulfiquer, F; Santhanam, G; Ahmed, M A S; Deeb, J
2012-01-01
An apparently well baby girl born at term was presented with signs and symptoms suggestive of acute onset of generalised floppiness at the age of 3 months. Clinically, the baby had lower motor neuron type of muscle weakness; detailed investigation lead to the diagnosis of neuromuscular junction disorder secondary to botulism toxicity. Further tests confirmed the botulism toxicity secondary to honey ingestion. The baby was treated with specific anticlostridium antibodies; she recovered remarkably, now growing and developing normally. PMID:22962382
Complete paralytic botulism mimicking a deep coma in a child.
Azapağası, Ebru; Kendirli, Tanıl; Öz-Tuncer, Gökçen; Albayrak, Pelin; Teber, Serap; Deda, Gülhis
2017-01-01
Botulism is a rare cause of neuroparalysis. Delay in diagnosis and treatment exerts adverse impact on mortality and morbidity. We report a child with complete flaccid paralysis followed by progression to coma-like consciousness. The patient required mechanical ventilation. As serological tests could not be performed, detailed history and physical examinations led to the suspicion of botulism, and repetitive nerve stimulation tests supported the diagnosis. Botulinum antitoxin was administered. The patient`s neuromuscular function improved rapidly.
Foodborne botulism in Poland in 2012.
Czerwiński, Michał; Czarkowski, Mirosław P; Kondej, Barbara
2014-01-01
The main objective of this article is to assess the epidemiology of foodborne botulism in Poland in 2012 compared to previous years, using national surveillance data. We reviewed surveillance data published in the annual bulletin "Infectious diseases and poisonings in Poland in 2012" and in previous publications, and botulism case reports for 2012 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. In 2012, a total of 22 foodborne botulism cases (including 9 laboratory confirmed cases) was reported, corresponding to the lowest annual incidence rate (0.06 per 100 000 population) since the introduction of botulism as mandatory notifiable disease. The highest incidence in the country was reported in Lubelskie (0.23) and Wielkopolskie (0.20). Incidence in rural areas (0.07 per 100 000 population) was slightly higher than the incidence in urban areas (0.05). Men had more than 2 times higher incidence than women; the highest incidence rate (0.20 per 100 000 population) was observed among men in the age group of 30-39 years. Most cases were associated with consumption of different types of commercially canned meat. Commercially canned fish was also a common vehicle. All cases were hospitalized. One death related to the disease was reported. In 2012, in Poland a downward trend in the incidence of foodborne botulism was maintained. From the point of view of national surveillance, it is necessary to increase the percentage of cases investigated with laboratory tests.
... foil-wrapped baked potatoes and oil infused with garlic. When you eat food containing the toxin, it ... not at room temperature. Store oils infused with garlic or herbs in the refrigerator. Infant botulism To ...
... potatoes cooked in foil, carrot juice, and chopped garlic in oil. Infant botulism occurs when a baby ... the refrigerator, not at room temperature. Oils with garlic or other herbs should also be refrigerated as ...
Walters, Maroya Spalding; Sreenivasan, Nandini; Person, Bobbie; Shew, Mark; Wheeler, Daniel; Hall, Julia; Bogdanow, Linda; Leniek, Karyn; Rao, Agam
2015-11-01
Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.
Cherington, Michael
2004-06-01
Botulism is both an old and an emerging disease. Over 100 years ago, the classic food-borne type was found to be caused by ingesting contaminated food containing the toxin produced by a bacteria. In the first half of the 20th century a second form, wound botulism, was discovered. Three additional forms (infant, hidden, and inadvertent) were first described in the last quarter of the 20th century. Our understanding of how botulinum toxin blocks the release of acetylcholine at the neuromuscular junction has been clarified in the past 10 years. In the past 20 years, we have witnessed one of the strangest of all ironies in the history of medicine. The very lethal botulinum toxin is now being used as a treatment in an expanding list of disorders. Research is advancing in several directions. These new avenues include improved methods of preventing and treating botulism and additional novel uses of botulinum toxin as a therapeutic agent. In this article, the five clinical forms of botulism, the actions of botulinum toxins, electrodiagnostic methods, treatments, and possible future directions are discussed. Copyright 2004 Thieme Medical Publishers, Inc.
Zhang, Jiu-Cong; Sun, Li; Nie, Qing-He
2010-11-01
Botulism is a neuroparalytic illness caused by botulinum toxin, a product of the Clostridium botulinum bacteria and characteristically presents as an acute, symmetrical, descending flaccid paralysis. Albeit it is the most poisonous substance known, which even poses a major threat as biological weapons, purified and highly diluted botulinum toxin can be used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain. There are six clinical presentations associated with current occurring botulism, each results from absorption of botulinum toxin into the bloodstream. The aim of this review is to summarize the current knowledge on the microbiology, epidemiology, vaccine research and clinical management of human botulism. Early diagnosis and management rely on history and physical examination. Delay in treatment may allow progression of paralysis, protracted hospitalization and deaths of long-term mechanical ventilation and intensive care unit care. The clinicians must take this disease into consideration of a possible outbreak. Awaiting laboratory confirmation is an egregious error, while awareness of the clinical sign and symptoms of botulism is critical for early diagnosis. Rapid management and followed public health surveillance may greatly alleviate disease severity and decrease mortality rates.
... and certain foods (such as honey and some corn syrups). Infant botulism occurs mostly in young infants ... spores. Clostridium spores are found in honey and corn syrup. These foods should not be fed to ...
Notes from the field: infant botulism caused by Clostridium baratii type F - Iowa, 2013.
Moodley, Amaran; Quinlisk, Patricia; Garvey, Ann; Kalas, Nicholas; Barash, Jason R; Khouri, Jessica M
2015-04-17
In June 2013, a male newborn aged 9 days (delivered after a full-term pregnancy) was brought to a hospital emergency department with a 2-day history of constipation, fussiness, and poor feeding. The mother reported her son's symptoms as excessive crying, reluctance to suck, and difficulty in swallowing milk. Within hours of arrival, the infant became less responsive and "floppy," and was intubated for respiratory failure. Infant botulism was suspected and Botulism Immune Globulin Intravenous (Human) (BIG-IV), licensed for the treatment of infant botulism types A and B, was administered on hospital day 2. Results of preliminary stool studies were reported positive for botulinum toxin type F on hospital day 3. Clostridium baratii type F was subsequently isolated in stool culture.
[Descending paralysis caused by wound botulism. A case report].
Hiersemenzel, L P; Jermann, M; Waespe, W
2000-02-01
We report on the history and clinical findings of an injecting drug abuser in the Canton of Zurich who presented with multiple deep abscesses in the arms and legs. A diagnosis of wound botulism was made based on his clinical presentation with a rapidly progressing descending paralysis starting at the cranial nerves, a neuromuscular junction disorder on neurophysiologic testing, and normal findings on lumbar puncture. Several cases of wound botulism have occurred in i.v. drug abuse in Switzerland since 1997. We suspect subcutaneous injections of contaminated heroin containing Clostridium spores as sites of entry. Wound botulism caused by Clostridium botulinum is a rare cause of rapidly progressing, generalized, flaccid paralysis and should be considered in patients with a history of i.v. drug abuse presenting with descending paralysis.
[Botulism in Osterdalen in 1831].
Schjønsby, Hans Petter
2002-12-10
The earliest report we have had of an outbreak of botulism in Norway is from 1934, of five cases caused by contaminated salted and dried ham. All patients survived. This paper describes an early outbreak of botulism in the county of Hedmark in 1831 on the basis of a previously unknown report to the county governor from district public health officer Peter Heiberg (1778-1849). Two cases were reported, one of them fatal. The contaminated food was salted and fermented trout or char.
Black Tar Heroin Skin Popping as a Cause of Wound Botulism.
Qureshi, Ihtesham A; Qureshi, Mohtashim A; Rauf Afzal, Mohammad; Maud, Alberto; Rodriguez, Gustavo J; Cruz-Flores, Salvador; Kassar, Darine
2017-12-01
Botulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. It is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. We present our observations with a descriptive case series of wound botulism secondary to black tar heroin (BTH) injection. We report a retrospective single-center case series of 15 consecutive cases of wound botulism presenting to University Medical Center of El Paso. Medical records where reviewed to obtain demographic information, clinical presentation, treatment, and outcome. We identified fifteen patients with mean age of 47 years: twelve men, and three women. All had administered BTH through skin popping and had abscesses in the administration areas. By history, the most common symptoms were dysphagia (66%), proximal muscle weakness of upper and lower extremity (60%), neck flexor muscle weakness (33%), ophthalmoplegia (53%), bilateral ptosis (46%), dysarthria (53%), double vision (40%), blurred vision (33%), and dry mouth (20%). During the examination, the most common features noted were: proximal muscle weakness of upper and lower extremities (73%), ophthalmoplegia (53%), ptosis (46%). In patients with documented wound botulism, the pupils were reactive in 46%. All patients required mechanical ventilation and were treated with the trivalent antitoxin. Eleven patients (73.3%) were discharged home, two were transferred to a skill nursing facility, and two were transferred to long-term acute care facility. In our patients, BTH injection, involving the action of injecting under the skin acetylated morphine derivatives (mostly 6-monoacetylmorphine and 3-monoacetylmorphine), was associated with the development of botulism. The availability of BTH at the US-Mexican border is not surprising since it is frequently produced in Latin America. Its association with the development of botulism should be recognized early to allow a prompt diagnosis and treatment with the antitoxin. A clinical feature worth noting is the presence of normal pupillary light reflex in nearly half of patients. Therefore, the presence of a normal pupillary response does not exclude the presence of wound botulism.
Fatal outbreak of botulism in Greenland.
Hammer, Tóra Hedinsdottir; Jespersen, Sanne; Kanstrup, Jakob; Ballegaard, Vibe Cecilie; Kjerulf, Anne; Gelvan, Allan
2015-03-01
Botulism commonly occurs when the anaerobic, gram-positive bacterium Clostridium botulinum, under suitable conditions, produces botulinum neurotoxins. Named A-F, these toxins are the immediate causative agent of the clinical symptoms of symmetrical, descending neurological deficits, including respiratory muscle paralysis. We present five cases of foodborne botulism occurring in Greenland, two with fatal outcome, caused by ingestion of tradionally preserved eider fowl. In the cases of the survivors, antitoxin and supportive care, including mechanical ventilation, were administered. In these cases recovery was complete. Microbiological assays, including toxin neutralization bioassay, demonstrated the presence of neurotoxin E in two survivors. The third survivor was shown by PCR to have the BoNT type E gene in faeces. This is the first report of cases of fatal botulism in Greenland. It underscores the importance of prompt coordinated case management effort in a geographically isolated area such as Greenland.
Molecular and Epidemiological Characterization of Infant Botulism in Beijing, China.
Dong, Yin Ping; Wang, Wei; Jiang, Tao; Xu, Jin; Han, Chun Hui; Yan, Shao Fei; Fanning, Séamus; Li, Ying; Ma, Xiao Chen; Zhang, Di; Zhao, Yao; Zeng, Biao; Li, Feng Qin
2017-06-01
Laboratory-based pathogen isolation, identification, and toxicity determination were performed on samples from a suspected case of infant botulism. Mice injected with cultures generated from the enema sample and ingested Powered infant formula (PIF) presented typical signs of botulism. Antitoxins to polyvalent botulinum neurotoxins (BoNTs) and monovalent BoNT type B antitoxin had protective effects. Clostridium botulinum isolated from the enema and residual PIF samples were positive for type B toxin. Pulsed-field gel electrophoresis (PFGE) revealed that the two strains of C. botulinum isolated from the two samples produced indistinguishable pulsotypes. These findings confirmed this case of type B infant botulism associated with the ingestion of PIF contaminated by type B C. botulinum spores. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Immunoproteomics Approach for Screening of Vaccine Candidates against Intestinal Botulism.
Sharma, Arti; Rani, Sarita; Alam, Syed Imteyaz; Ponmariappan, Sarkaraisamy
2017-01-01
Intestinal botulism is an infectious form of botulism in which disease results from ingesting spores, which is followed by spore germination and intraluminal production of botulinum neurotoxins over an extended period. Botulinum neurotoxin is produced by endospore forming bacteria called C. botulinum. Immunoproteomic study was used to screen the cross reactive immunogenic proteins of Clostridium botulinum type B using C. botulinum type B live spore antiserum. The whole cell proteins were separated by two dimensional gel electrophoresis and transferred to polyvinylidene difluoride membranes. Further, the Western blotting was performed with mouse pups immune serum against C. botulinum type B live spores. Eight predominant cross immunoreactive proteins were identified by mass spectrometry. These immunogenic proteins might be used to develop novel subunit vaccine candidates against the intestinal botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
van der Vorst, Maria M J; Jamal, Wafaa; Rotimi, Vincent O; Moosa, Alie
2006-01-01
To report the first case of infant botulism in Arabian Gulf States. A 6-week-old infant, presenting with signs of sepsis, was intubated and ventilated due to progressive weakness. Infant botulism was suspected with acute flaccid paralysis and a history of honey consumption. An electromyogram showed decreased amplitude of compound muscle action potential in all motor nerves, preserved sensory responses; the motor terminal latencies and motor conduction velocities were normal. Blood, stool and honey samples were sent for culture. Stool and honey cultures showed two identical strains of Clostridium botulinum. This case shows that the infant botulism occurred from the ingested contaminated honey. Hence vigilance should be maintained when a baby is fed honey and shows signs of progressive weakness because the disease can quickly progress to respiratory failure.
Infant botulism: case reports and review.
Krishna, S; Puri, V
2001-04-01
Infant Botulism (IB) is a relatively uncommon, though potentially life-threatening neuroparalytic illness caused by the toxins elaborated by Clostridium botulinum (C botulinum). We describe two cases of Infant Botulism. Both these infants presented with a sepsis-like picture and were unsuspectingly treated with the conventional antibiotics ampicillin and gentamicin. The neuroparalytic syndrome of both infants was probably potentiated by the use of gentamicin. We suggest that cefotaxime be carefully considered instead of gentamicin in the initial management of infants presenting with a sepsis-like clinical picture and associated history of constipation, recent onset of hypotonia, poor feeding and/or drooling. Clinical trials evaluating human Botulism Immune Globulin (BIG) are under way by the California Department of Health. This article comes at a very timely moment because once FDA approved, BIG will be the only specific treatment available for this illness.
An outbreak of type C botulism in waterbirds: Incheon, Korea.
Shin, Na-Ri; Byun, Seong Hwan; Chun, Jeong Hoon; Shin, Jeong Hwa; Kim, Yun Jeong; Kim, Jeong-Hee; Rhie, Gi-Eun; Chung, Hyen Mi; Mo, In-Pil; Yoo, Cheon-Kwon
2010-07-01
Five outbreaks of botulism in waterbirds were encountered over a 5-yr period from 2004 to 2008 in Korea. In October 2008, an outbreak of avian type C botulism affected approximately 2,000 wild waterbirds in the Namdong flood control basin, Incheon, South Korea. Ecologic conditions, clinical signs exhibited by moribund birds, and lack of gross pathology and microbial evidence of infectious disease, suggested botulinum intoxication. Type C botulinum toxin was demonstrated in duck sera, liquid culture of intestinal tissue, and an extract of maggots taken from the carcasses. Additionally, 34 of 40 (85.0%) sediment samples from the same area were positive for botulinum toxin by mouse bioassay using multivalent (types A-F) antiserum, indicating that toxigenic Clostridium botulinum was present in the environment. This is the most severe case of avian botulism documented in Korea.
Foodborne botulism in Poland in 2111.
Czerwiński, Michał; Czarkowski, Mirosław P; Kondej, Barbara
2013-01-01
The main objective of this article is to assess the epidemiology of foodborne botulism in Poland in 2011, using national surveillance data. We reviewed surveillance data published in the annual bulletin "Infectious diseases and poisonings in Poland" from 2005 to 2011, and botulism case reports from 2011 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. In 2011, a total of 35 foodborne botulism cases (including 21 laboratory confirmed cases) was reported, corresponding to the one of the lowest annual incidence rate (0.09 per 100,000 population) since the introduction of botulism as mandatory notifiable disease. The higher incidence rates compared to the previous year were in the Warmińsko-Mazurskie, Kujawsko-Pomorskie, Lubelskie, Podkarpackie, Mazowieckie and Dolnoślaskie. Incidence in rural areas (0.13 per 100,000 population) was higher than the incidence in urban areas (0.07). Men, had more than 3,5 times higher incidence than women; the highest incidence rate (0.23 per 100,000 population) was observed among men in the age group of 60 + years. Most cases were associated with consumption of commercially canned meat (including pork and other types of meat). Home canned foods containing meats or vegetables and meats were also a common vehicle. Almost all cases were hospitalized (33 cases). One death related to the disease was reported. In 2011, in Poland epidemiology of the foodborne botulism remains stable. From the point of view of national surveillance, it is necessary to increase the percentage of cases investigated with laboratory tests.
Foodborne botulism in Poland in 2013.
Czerwiński, Michał; Czarkowski, Mirosław P; Kondej, Barbara
2015-01-01
The aim of the study is to assess the epidemiology of foodborne botulism in Poland in 2013. We reviewed surveillance data published in the annual bulletin "Infectious diseases and poisonings in Poland in 2013" and in previous publications, and botulism case reports for 2013 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. In 2013, a total of 24 foodborne botulism cases (including 8 laboratory confirmed cases) was reported, corresponding to the lowest annual incidence rate (0.06 per 100,000 population) since the introduction of botulism as mandatory notifiable disease. The highest incidence in the country was reported in Kujawsko-Pomorskie (0.19). Incidence in rural areas (0.09 per 100,000 population) was more than 2-fold higher than the incidence in urban areas (0.04). Men, had more than 3 times higher incidence than women; the highest incidence rate (0.29 per 100,000 population) was observed among men in the age group of 40-49 years. Most cases were associated with consumption of different types of commercially canned meat. Commercially canned fish was also a common vehicle. All cases were hospitalized. No deaths related to the disease were reported. In 2013, in Poland a downward trend in the incidence of foodborne botulism was maintained. Insufficient laboratory capacity remains a major weakness in national surveillance resulting in disproportionate reporting of cases meeting only clinical criteria and an epidemiological link. This situation clearly speaks for the need to improve laboratory capacity for surveillance.
Sreenivasan, Nandini; Person, Bobbie; Shew, Mark; Wheeler, Daniel; Hall, Julia; Bogdanow, Linda; Leniek, Karyn; Rao, Agam
2015-01-01
Objectives. Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. Methods. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. Results. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. Conclusions. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks. PMID:26378846
Rocke, Tonie E.; Euliss, Ned H.; Samuel, Michael D.
1999-01-01
Avian botulism is an important disease affecting many species of waterbirds in North America, but the environmental conditions that initiate outbreaks are poorly understood. To determine wetland attributes associated with outbreaks of avian botulism in waterbirds at the Sacramento National Wildlife Refuge (SNWR), California, we compared environmental characteristics between wetlands where outbreaks occurred (outbreak wetlands) and did not occur (nonoutbreak wetlands). In June through October, 1987 89, we monitored the occurrence of avian botulism via observations for sick or dead sentinel mallards (Anas platyrhynchos) placed in 4 wetland enclosures. During this same time period, we collected environmental data from the water column and sediments of each wetland enclosure at 10 14-day sampling intervals. Multivariate analysis was used to reduce 22 environmental variables to 7 factors for inclusion in subsequent statistical analyses. We found that outbreak wetlands had significantly lower redox potential than nonoutbreak wetlands. The probability of botulism in sentinel mallards was associated with increasing temperature, increasing invertebrate abundance or biomass, and decreasing turbidity. However, because these factors were not consistently higher in outbreak wetlands compared to nonoutbreak wetlands, they may have a more proximate effect in initiating an outbreak.
Anniballi, Fabrizio; Fillo, Silvia; Giordani, Francesco; Auricchio, Bruna; Tehran, Domenico Azarnia; di Stefano, Enrica; Mandarino, Giuseppina; De Medici, Dario; Lista, Florigio
2016-12-01
Clostridium botulinum is the bacterial agent of botulism, a rare but severe neuro-paralytic disease. Because of its high impact, in Italy botulism is monitored by an ad hoc surveillance system. The National Reference Centre for Botulism, as part of this system, collects and analyzes all demographic, epidemiologic, microbiological, and molecular data recovered during cases and/or outbreaks occurred in Italy. A panel of 312 C. botulinum strains belonging to group I were submitted to MLVA sub-typing. Strains, isolated from clinical specimens, food and environmental samples collected during the surveillance activities, were representative of all forms of botulism from all Italian regions. Through clustering analysis isolates were grouped into 12 main clusters. No regional or temporal clustering was detected, demonstrating the high heterogeneity of strains circulating in Italy. This study confirmed that MLVA is capable of sub-typing C. botulinum strains. Moreover, MLVA is effective at tracing and tracking the source of contamination and is helpful for the surveillance system in terms of planning and upgrading of procedures, activities and data collection forms. Copyright © 2016 Elsevier B.V. All rights reserved.
Rocke, Tonie E.; Euliss, Ned H.; Samuel, Michael D.
1999-01-01
Avian botulism is an important disease affecting many species of waterbirds in North America, but the environmental conditions that initiate outbreaks are poorly understood. To determine wetland attributes associated with outbreaks of avian botulism in waterbirds at the Sacramento National Wildlife Refuge (SNWR), California, we compared environmental characteristics between wetlands where outbreaks occurred (outbreak wetlands) and did not occur (nonoutbreak wetlands). In June through October 1987-89, we monitored the occurrence of avian botulism via observations for sick or dead sentinel mallards (Anas platyrhynchos) placed in 4 wetland enclosures. During this same time period, we collected environmental data from the water column and sediments of each wetland enclosure at 10-14-day sampling intervals. Multivariate analysis was used to reduce 22 environmental variables to 7 factors for inclusion in subsequent statistical analyses. We found that outbreak wetlands had significantly lower redox potential than nonoutbreak wetlands. The probability of botulism in sentinel mallards was associated with increasing temperature, increasing invertebrate abundance or biomass, and decreasing turbidity. However, because these factors were not consistently higher in outbreak wetlands compared to nonoutbreak wetlands, they may have a more proximate effect in initiating an outbreak.
Therapeutic management of botulism in dairy cattle.
Pandian, S Jegaveera; Subramanian, M; Vijayakumar, G; Balasubramaniam, G A; Sukumar, K
2015-11-01
To report the successful recovery of few dairy cattle from botulism in response to a modified therapeutic strategy. Seventy four naturally-occurring clinical cases of bovine botulism encountered during the period of 2012-2014 which were confirmed by mouse lethality test became material for this study. Affected animals were made into three groups based on the treatment modifications made during the course of study. With the modified therapeutic regimen, 17 animals recovered after 7-10 days of treatment. Clinical recovery took 2-30 days. Animals which were not given intravenous fluid and calcium recovered uneventfully. Cattle which were already treated with intravenous fluids, calcium borogluconate, and antibiotics did not recover. They were either died or slaughtered for salvage. In cattle with botulism, administration of Vitamin AD3E and activated charcoal aid the clinical recovery. Besides, strictly avoiding anti-clostridial antibiotics, fluid therapy, and calcium therapy may facilitate the clinical recovery. Upon fluid administration, the pulmonary congestion existed in the ailing cattle might have worsened the anoxia. Administration of antibiotics like penicillin, aminoglycosides, and tetracyclines further worsen the neuronal paralysis by increasing the availability of botulinum neurotoxin. Cattle in early botulism have fair chances of recovery with the modified therapy.
Anlar, O; Irmak, H; Tombul, T; Akdeniz, H; Caksen, H; Kose, D; Ceylan, A
2003-09-01
Food-borne botulism is an acute form of poisoning that results from ingestion of a toxin produced by Clostridium botulinum. Botulism toxin causes its major effect by blocking neuromuscular transmission in autonomic and motor nerve terminals. In this study, we present the features of eleven cases of food-borne botulism admitted to our hospital in 2001. All of the cases were caused by home-prepared foods; green beans. In these cases, the main symptoms and signs were generalized muscular weakness, dry mouth, dysphagia, disponea and diplopia. Electrophysiological studies were performed on four patients. Motor conduction studies showed that compound muscle action potentials were decreased with normal latencies and conduction velocities. The needle electromyography showed signs of denervation potentials like fibrillation and positive waves in four patients. Repetitive nerve stimulation with high frequency (20 Hz) induced an increment close to 100% in the amplitudes in 2 of 4 patients. Although toxin could not be detected in the patients, the electromyographic findings supported our diagnosis. We concluded that electromyography has an important role in diagnosis of botulism, especially in the condition that serologic tests are negative or cannot be performed.
The status of botulism as a world health problem
Meyer, K. F.
1956-01-01
The author reviews the international literature and brings up to date the published statistical data on botulism—a disease which, owing to its spectacular nature and high case-fatality rate, appears to occupy a place out of proportion to its frequency as a cause of death in some regions. Without exception, botulism is caused by carelessness in the preparation and preservation of vegetable and animal foods. Local customs of eating such food uncooked, in the form of salads, watery conserves, poorly cured or inadequately smoked pork and salted fish products create the botulism problem. The risk of botulism exists wherever the telluric incidence of Type A, B, and E spores is high. Surveys to appraise the extent of Clostridium botulinum in the soils of Asia and Africa are urgently needed so that the magnitude of the potential problem in these areas can be properly evaluated. Food processors must not relax in the use of properly calculated thermal processes now available for every food commodity. Agencies that promote or give instruction in preservation of food in the home should be thoroughly familiar with the most effective, practical, and inexpensive methods of preventing botulism. PMID:13383365
Clostridium botulinum in cattle and dairy products.
Lindström, Miia; Myllykoski, Jan; Sivelä, Seppo; Korkeala, Hannu
2010-04-01
The use of plastic-wrapped and nonacidified silage as cattle feed has led to an increasing number of botulism outbreaks due to Clostridium botulinum Groups I-III in dairy cattle. The involvement of Groups I and II organisms in cattle botulism has raised concern of human botulism risk associated with the consumption of dairy products. Multiplication of C. botulinum in silage and in the gastrointestinal tract of cattle with botulism has been reported, thus contamination of the farm environment and raw milk, and further transmission through the dairy chain, are possible. The standard milk pasteurization treatment does not eliminate spores, and the intrinsic factors of many dairy products allow botulinal growth and toxin production. Although rare, several large botulism outbreaks due to both commercial and home-prepared dairy products have been reported. Factors explaining these outbreaks include most importantly temperature abuse, but also unsafe formulation, inadequate fermentation, insufficient thermal processing, post-process contamination, and lack of adequate quality control for adjunct ingredients were involved. The small number of outbreaks is probably explained by a low incidence of spores in milk, the presence of competitive bacteria in pasteurized milk and other dairy products, and growth-inhibitory combinations of intrinsic and extrinsic factors in cultured and processed dairy products.
Botulism outbreak causes high mortality in Scottish cattle.
2017-11-11
SAc C VS disease Surveillance report for july 2017 Botulism in finishing cattleSeasonal dermatitis in Cheviot ewes Streptococcus suis type 2 meningitis and septicaemia in pigletsRodenticide toxicity in chickens. British Veterinary Association.
An outbreak of type E botulism among common loons (Gavia immer) in Michigan's Upper Peninsula
Brand, Christopher J.; Schmitt, Stephen; Duncan, Ruth M.; Cooley, Thomas M.
1988-01-01
An epizootic of type E botulism (Clostridium botulinum) occurred among common loons (Gavia immer) along the Lake Michigan shore of Michigan's Upper Peninsula (USA) during October and November 1983. An estimated 592 dead loons washed ashore along the Garden Peninsula. Type E botulinal toxin was demonstrated in blood samples and stomach contents of dead loons, and in samples of three species of dead fish found on the Lake Michigan shore. We suspect that loons acquired botulism by ingesting sick or dead fish containing type E toxin.
2008-04-02
Associated with Botulism Arvind Raghunath ,1 Francesc Perez-Branguli,1 Leonard Smith,2 and J. Oliver Dolly1 1International Centre for Neurotherapeutics...NUMBER 6. AUTHOR(S) Raghunath A Branguli FP Smith L Dolly JO 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION...Neurosci., April 2, 2008 • 28(14):3683–3688 Raghunath et al. • Botulism Combated by Gene Transfer of Mutated S25 horns, containing the cell bodies
Food-borne botulism in Japan in March 2012.
Momose, Yoshika; Asakura, Hiroshi; Kitamura, Masaru; Okada, Yumiko; Ueda, Yutaka; Hanabara, Yutaro; Sakamoto, Tomohiro; Matsumura, Tsuyoshi; Iwaki, Masaaki; Kato, Haru; Shibayama, Keigo; Igimi, Shizunobu
2014-07-01
In March 2012, two patients were transported urgently to the hospital in Tottori Prefecture, Japan, because of symptoms suggestive of botulism. Botulinum neurotoxin type A was detected in the clinical specimens and the food consumed by the two patients (vacuum packed adzuki-batto, a sweet adzuki bean soup containing noodles). We were able to make a prompt diagnosis of food botulism associated with the consumption of adzuki-batto, from which the causative pathogen Clostridium botulinum Ab was cultured. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Foodborne botulism associated with home-preserved turnip tops in Italy.
Anniballi, Fabrizio; Chironna, Elisa; Astegiano, Sara; Fiore, Alfonsina; Auricchio, Bruna; Buonincontro, Giuseppina; Corvonato, Maria; Segala, Vincenzo; Mandarino, Giuseppina; De Medici, Dario; Decastelli, Lucia
2015-01-01
In Italy, foodborne botulism is a rare disease mainly due to home-preserved food. In the case reported here, clinical diagnosis was performed on the basis of clinical signs and referred consumption of home-preserved turnip tops in oil. Definitive diagnosis was performed by detection of botulinum toxin in sera and neuro-toxigenic organisms in stools and leftover food. This case report highlights the need of a high medical awareness, prompt clinical diagnosis, and synergic collaboration among the health authorities for a correct management of botulism as well as disease containment.
The first case of type B infant botulism in Japan.
Kakinuma, H; Maruyama, H; Takahashi, H; Yamakawa, K; Nakamura, S
1996-10-01
A six-month-old girl with a 5 consecutive day history of constipation and poor feeding developed generalized weakness, poor head control, difficulties in sucking and swallowing, and cranial nerve dysfunction within a few days. These characteristic manifestations and clinical course prompted examination of the possibility of infant botulism, although no history of eating honey was obtained. Mouse bioassay performed with enema effluent demonstrated type B botulinum toxin. Culture of the effluent was positive for Clostridium botulinum type B. This is the first case of type B infant botulism in Japan.
Botulism as a food poisoning: what is it?
El-Bahnasawy, Mamdouh M; Aly, Nagwa Zein-El-Abdeen; Abdel-Fattah, Magda Abdel Hameed; Morsy, Tosson A
2014-04-01
Botulism is a rare but potentially life-threatening neuroparalytic syndrome resulting from the action of a neurotoxin elaborated by the microorganism Clostridium botulinum. This disease has a lengthy history; the first investigation of botulism occurred in the 1820s with a case report on hundreds of patients with "sausage poisoning" in a southern German town. Several decades later in Belgium, the association was demonstrated between a neuromuscular paralysis and ham infected by a spore forming bacillus that was isolated from the ham. The organism was named Bacillus botulinus after the Latin word for sausage, botulus.
Botulism associated with commercially canned chili sauce--Texas and Indiana, July 2007.
2007-08-03
On July 7 and July 11, 2007, public health officials in Texas and Indiana, respectively, reported to CDC four suspected cases of foodborne botulism, two in each state. Investigations conducted by state and local health departments revealed that all four patients had eaten brands of Castleberry's hot dog chili sauce before illness began. Botulinum toxin type A was detected in the serum of one Indiana patient and in a leftover chili mixture obtained from his home. CDC informed the Food and Drug Administration (FDA) of the apparent link between illness and consumption of the chili sauce. On July 18, FDA issued a consumer advisory, and the manufacturer, Castleberry's Food Company (Augusta, Georgia), subsequently recalled the implicated brand and several other products produced in the same set of retorts (commercial-scale pressure cookers for processing canned foods) at the same canning facility. Examination of the canning facility in Georgia during the outbreak investigation had identified deficiencies in the canning process. On July 19, the U.S. Department of Agriculture Food Safety and Inspection Service (FSIS) issued a press release that announced a recall of chili and certain meat products from the Castleberry canning facility and provided recommendations to consumers. That recall was expanded on July 21 to include additional canned products. A fifth case of botulism potentially linked to one of the recalled products is under investigation in California. This report describes the ongoing investigation by members of OutbreakNet and others and the measures undertaken to control the outbreak, which is the first outbreak of foodborne botulism in the United States associated with a commercial canning facility in approximately 30 years. Clinicians should be vigilant for symptoms of botulism, including symmetric cranial nerve palsies, especially if accompanied by descending flaccid paralysis. Consumers should not eat any of the recalled chili sauce or other recalled products and should carefully dispose of all recalled products. Information regarding product disposal is available at http://www.cdc.gov/botulism/botulism_faq.htm.
Opila, Tamara; George, Asha; El-Ghanem, Mohammad; Souayah, Nizar
2017-02-01
New therapeutic strategies, including immune globulin intravenous, have emerged in the past two decades for the management of botulism. However, impact on outcomes and hospitalization charges among infants (aged ≤1 year) with botulism in the United States is unknown. We analyzed the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) for in-hospital outcomes and charges for infant botulism cases from 1997 to 2009. Demographics, discharge status, mortality, length of stay, and hospitalization charges were reported from the two databases and compared. Between 1997 and 2009, 504 infant hospitalizations were captured in KID', and 340 hospitalizations from NIS, for comparable years. A significant decrease was observed in mean length of stay for 'KID (P < 0.01); a similar decrease was observed for the NIS. The majority of patients were discharged to home. Despite an initial decrease after 1997, an increasing trend was observed for 'KID/NIS mean hospital charges from 2000 to 2009 (from $57,659/$56,309 to $143,171/$106,378; P < 0.001/P < 0.001). A linear increasing trend was evident when examining mean daily hospitalization charges for both databases. In conducting a subgroup analysis of the 'KID database, the youngest patients with infantile botulism (≤1.9 months) displayed the highest average number of procedures during their hospitalization (P < .001) and the highest rate of mechanical ventilation (P < .001), compared with their older counterparts. Infant botulism cases have demonstrated a significant increase in hospitalization charges over the years despite reduced length of stay. Additionally, there were significantly higher daily adjusted hospital charges and an increased rate of routine discharges for immune globulin intravenous-treated patients. More controlled studies are needed to define the criteria for cost-effective use of intravenous immune globulin in the population with infant botulism. Copyright © 2016 Elsevier Inc. All rights reserved.
McGorum, B C; Scholes, S; Milne, E M; Eaton, S L; Wishart, T M; Poxton, I R; Moss, S; Wernery, U; Davey, T; Harris, J B; Pirie, R S
2016-11-01
Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxico-infection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Descriptive study. Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein-25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted. © 2015 EVJ Ltd.
... if a baby younger than 1 year eats honey, so it's important that babies don't eat honey until they're older. What Does Botulism Do? ... remind grown-ups that babies shouldn't have honey. There's one more thing kids can do to ...
Efficacy of a type C botulism vaccine in green-winged teal.
Rocke, T E; Samuel, M D; Swift, P K; Yarris, G S
2000-07-01
We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.
Two cases of foodborne botulism with home-preserved asparagus.
Zanon, P; Pattis, P; Pittscheider, W; Roscia, G; De Giorgi, G; Sacco, G; Vötter, K; Stockner, I; De Giorgi, F; Wiedermann, C J
2006-03-01
Botulism is a rare but potentially fatal disease caused by toxins produced by Clostridium botulinum. We report botulism in two adult females, one of them just tasting from "bad" asparagus and the other eating the full portion. Both patients survived after intermittent mechanical ventilation and trivalent antitoxin administration. The diagnosis was confirmed by detection of botulinum toxin. Acute onset of bilateral cranial neuropathies associated with symmetric descending weakness as well as some key features of the botulism syndrome including absence of fever, symmetric neurologic deficits, the patients remaining responsive and no sensory deficits, with the exception of blurred vision, led to the clinical diagnosis in the first presenting case which was then easily made in the second. Despite the fact that amount of toxin ingested, time-to-symptom development, and time-to-recovery markedly differed in the two patients, their maximal disease severity was similar.
The first case of a major avian type C botulism outbreak in Poland.
Wlodarczyk, Radoslaw; Minias, Piotr; Kukier, Elibieta; Grenda, Tomasz; Smietanka, Krzysztof; Janiszewski, Tomasz
2014-09-01
Major outbreaks of avian type C botulism have been rarely reported from Central Europe. In this paper, we report the first severe outbreak of avian type C botulism in Poland. In 2011-12, two epizootics caused by Clostridium botulinum took place at Jeziorsko dam reservoir and affected an estimated number of 5500 birds in 2011 and 1600 birds in 2012. In total, 24 species ofwaterbirds were affected, including mainly waterfowl (37.0%), shorebirds (27.0%), rallids (25.7%), and larids (9.1%). Mallards (Anas platyrhynchos) and coots (Fulica atra) were most commonly represented among all affected species (27.5% and 25.0% of all recorded carcasses, respectively). Laboratory analyses confirmed the presence of type C botulinum toxin in the internal organs of paralyzed birds. This case study from the Jeziorsko dam reservoir demonstrates that this type of shallow-water habitat is especially prone to avian botulism outbreaks in the climatic conditions of Central Europe.
Intestinal toxemia botulism in 3 adults, Ontario, Canada, 2006-2008.
Sheppard, Yolanda D; Middleton, Dean; Whitfield, Yvonne; Tyndel, Felix; Haider, Shariq; Spiegelman, Jamie; Swartz, Richard H; Nelder, Mark P; Baker, Stacey L; Landry, Lisa; Maceachern, Ross; Deamond, Sherri; Ross, Lorrie; Peters, Garth; Baird, Michelle; Rose, David; Sanders, Greg; Austin, John W
2012-01-01
Five cases of intestinal toxemia botulism in adults were identified within an 18-month period in or near Toronto, Ontario, Canada. We describe findings for 3 of the 5 case-patients. Clinical samples contained Clostridium botulinum spores and botulinum neurotoxins (types A and B) for extended periods (range 41-61 days), indicative of intestinal toxemia botulism. Patients' clinical signs improved with supportive care and administration of botulinum antitoxin. Peanut butter from the residence of 1 case-patient yielded C. botulinum type A, which corresponded with type A spores found in the patient's feces. The food and clinical isolates from this case-patient could not be distinguished by pulsed-field gel electrophoresis. Two of the case-patients had Crohn disease and had undergone previous bowel surgery, which may have contributed to infection with C. botulinum. These cases reinforce the view that an underlying gastrointestinal condition is a risk factor for adult intestinal toxemia botulism.
Avian botulism--another perspective.
Wobeser, G
1997-04-01
Waterfowl botulism is unique among intoxications because toxin produced within its victims leads to secondary poisoning of other birds. Because of this phenomenon, the epizootiology of the carcass-maggot cycle of botulism resembles that of an infectious disease and the reproductive rate (R) of the disease could be defined as the average number of secondary intoxications attributable to a single carcass introduced into a marsh. I propose that toxin production and botulism occur commonly at a low level in many marshes and that factors which influence R determine when the disease expands into a large epizootic. A model that incorporates the number of carcasses occurring in a marsh, the probability of a carcass containing spores, the probability of a carcass persisting until toxin-bearing maggots emerge, and the contact rate between live birds and toxin, may be useful for predicting the extent of secondary poisoning, for identifying questions for research, and as a theoretical basis for management.
Foodborne Botulism in Canada, 1985–2005
Leclair, Daniel; Fung, Joe; Isaac-Renton, Judith L.; Proulx, Jean-Francois; May-Hadford, Jennifer; Ellis, Andrea; Ashton, Edie; Bekal, Sadjia; Farber, Jeffrey M.; Blanchfield, Burke
2013-01-01
During 1985–2005, a total of 91 laboratory-confirmed outbreaks of foodborne botulism occurred in Canada; these outbreaks involved 205 cases and 11 deaths. Of the outbreaks, 75 (86.2%) were caused by Clostridium botulinum type E, followed by types A (7, 8.1%) and B (5, 5.7%). Approximately 85% of the outbreaks occurred in Alaska Native communities, particularly the Inuit of Nunavik in northern Quebec and the First Nations population of the Pacific coast of British Columbia. These populations were predominantly exposed to type E botulinum toxin through the consumption of traditionally prepared marine mammal and fish products. Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants. Improvements in botulism case identification and early treatment have resulted in a reduction in the case-fatality rate in Canada. PMID:23735780
Efficacy of a type C botulism vaccine in green-winged teal
Rocke, T.E.; Samuel, M.D.; Swift, P.K.; Yarris, G.S.
2000-01-01
We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.
Foodborne botulism in Canada, 1985-2005.
Leclair, Daniel; Fung, Joe; Isaac-Renton, Judith L; Proulx, Jean-Francois; May-Hadford, Jennifer; Ellis, Andrea; Ashton, Edie; Bekal, Sadjia; Farber, Jeffrey M; Blanchfield, Burke; Austin, John W
2013-06-01
During 1985-2005, a total of 91 laboratory-confirmed outbreaks of foodborne botulism occurred in Canada; these outbreaks involved 205 cases and 11 deaths. Of the outbreaks, 75 (86.2%) were caused by Clostridium botulinum type E, followed by types A (7, 8.1%) and B (5, 5.7%). Approximately 85% of the outbreaks occurred in Alaska Native communities, particularly the Inuit of Nunavik in northern Quebec and the First Nations population of the Pacific coast of British Columbia. These populations were predominantly exposed to type E botulinum toxin through the consumption of traditionally prepared marine mammal and fish products. Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants. Improvements in botulism case identification and early treatment have resulted in a reduction in the case-fatality rate in Canada.
Medical treatment for botulism.
Chalk, Colin H; Benstead, Tim J; Keezer, Mark
2014-02-20
Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear. This is an update of a review first published in 2011. To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism. On 30 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register (30 March 2013), CENTRAL (2013, Issue 3) in The Cochrane Library, MEDLINE (January 1966 to March 2013) and EMBASE (January 1980 to March 2013). We reviewed bibliographies and contacted authors and experts. Randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine. Two authors independently selected studies, assessed risk of bias and extracted data onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events. A single randomized controlled trial met the inclusion criteria. We found no additional trials when we updated the searches in 2013. This trial evaluated human-derived botulinum immune globulin (BIG) for the treatment of infant botulism and included 59 treatment participants as well as 63 control participants. The control group received a control immune globulin which did not have an effect on botulinum toxin. In this trial there was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among those participants admitted to the intensive care unit (ICU) and mechanically ventilated, but overall we judged the risk of bias to be low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on mean duration of hospitalization (BIG: 2.60 weeks, 95% CI 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) 3.10 weeks, 95% CI 1.68 to 4.52), mechanical ventilation (BIG: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (BIG: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (BIG: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11). There is evidence supporting the use of human-derived botulinum immune globulin (BIG) in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding with BIG treatment. This evidence was of moderate quality for effects on duration of mechanical ventilation but was otherwise of high quality. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.
Recurrent wound botulism among injection drug users in California.
Yuan, Jean; Inami, Gregory; Mohle-Boetani, Janet; Vugia, Duc J
2011-04-01
Botulism is an acute neurologic illness characterized by cranial nerve palsies and descending flaccid paralysis. Botulism is a rare disease and recurrent botulism even more rare. We review cases of recurrent wound botulism (WB) among injection drug users (IDUs) in California from 1993 through 2006 and describe 2 case patients. From botulism surveillance data for 1993-2006, we identified patients with >1 episode of clinical WB, defined as acute descending paralysis with a visible wound or recent history of injection drug use. For each patient, ≥1 of their WB episodes was laboratory confirmed. We extracted demographic, clinical, and laboratory information from case and laboratory reports and compared clinical characteristic frequency of initial and second WB episodes. During 1993-2006, 17 IDUs had recurrent WB, 14 with 1 recurrence and 3 with 2 recurrences. Of 25 laboratory-confirmed episodes, 22 were confirmed through serum testing and 3 through wound testing. Patients were 32-61 years old, and 94% were male. All patients reported heroin injections; 88% specified black tar heroin use and 76% reported subcutaneous injection. The most common presentations were having a visible wound, speech difficulty, double vision, respiratory difficulty, and trouble swallowing. There were no significant differences in clinical presentation between initial and second episodes. As the California epidemic of WB among IDUs continues, WB episodes are recurring. Both clinicians and IDUs should be aware of the potential for WB to recur among IDUs to enable timely diagnosis and early botulinum antitoxin administration and supportive care. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2010-07-15
obligate approximately $2 billion to acquire countermeasures against anthrax, botulism , radiation, and smallpox. The HHS has also employed the...these contracts to purchase treatments for botulism and internal radioactive particle contamination. See U.S. Government Accountability Office
Pandemic Flu and Medical Biodefense Countermeasure Liability Limitation
2010-02-12
covering countermeasures against other strains of influenza (including H1N1), anthrax, botulism , small pox, and acute radiation syndrome...Secretary of HHS has issued additional declarations covering various countermeasures against anthrax, botulism , acute radiation syndrome, smallpox, and
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2010-07-02
market to obligate approximately $2 billion to acquire countermeasures against anthrax, botulism , radiation, and smallpox. The HHS has also...Acquisitions”). The HHS used these contracts to purchase treatments for botulism and internal radioactive particle contamination. See U.S. Government
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2010-07-07
obligate approximately $2 billion to acquire countermeasures against anthrax, botulism , radiation, and smallpox. The HHS has also employed the...used these contracts to purchase treatments for botulism and internal radioactive particle contamination. See U.S. Government Accountability Office
Garlic-in-oil associated botulism: episode leads to product modification.
Morse, D L; Pickard, L K; Guzewich, J J; Devine, B D; Shayegani, M
1990-01-01
In February 1989, three cases of botulism occurred in persons who consumed garlic bread made from a garlic-in-oil product. Testing of leftover garlic-in-oil showed it to have a pH of 5.7 and to contain high concentrations of Clostridium botulinum organisms and toxin. This was the second episode of botulism associated with a low acid garlic-in-oil product which needs constant refrigeration. In response, the Food and Drug Administration has taken steps to prevent a recurrence by requiring that microbial inhibitors or acidifying agents be added to such products. PMID:2240308
Mechanical ventilation and management of an adult horse with presumptive botulism.
Taylor, Sandra D; Toth, Balazs; Townsend, Wendy M; Bentley, Robin Timothy
2014-01-01
To describe the clinical course, management, and outcome of a horse with a presumptive diagnosis of botulism treated with long-term mechanical ventilation. A 6-year-old Quarter Horse gelding with a history of esophageal obstruction was evaluated for progressive tetraparesis. Generalized and progressive skeletal muscle weakness characterized by recumbency, decreased tongue, tail, eyelid, and anal tone, and respiratory failure was observed. Anticholinergic signs including decreased salivation, xerophthalmia, and ileus were also noted. A presumptive diagnosis of botulism was made, although mouse inoculation and spore identification testing were negative. Pentavalent botulism antitoxin was administered on Day 3. The horse was maintained on a water mattress and was managed with mechanical ventilation for 2 weeks. Complications encountered included necrotic rhinitis, intertrigo, decubital ulceration, jugular and cephalic vein thrombophlebitis, corneal ulceration, and transient ventricular tachycardia. The horse showed marked improvement in skeletal muscle strength and parasympathetic nervous system function, allowing it to be successfully weaned from the ventilator but suffered large colon volvulus on Day 21 and was euthanized. To the authors' knowledge, this is the first report of successful weaning from long-term mechanical ventilation and management of recumbency using a water mattress in an adult horse with presumptive botulism. © Veterinary Emergency and Critical Care Society 2014.
Shelley, E B; O'Rourke, D; Grant, K; McArdle, E; Capra, L; Clarke, A; McNamara, E; Cunney, R; McKeown, P; Amar, C F L; Cosgrove, C; Fitzgerald, M; Harrington, P; Garvey, P; Grainger, F; Griffin, J; Lynch, B J; McGrane, G; Murphy, J; Ni Shuibhne, N; Prosser, J
2015-02-01
We describe two cases of infant botulism due to Clostridium butyricum producing botulinum type E neurotoxin (BoNT/E) and a previously unreported environmental source. The infants presented at age 11 days with poor feeding and lethargy, hypotonia, dilated pupils and absent reflexes. Faecal samples were positive for C. butyricum BoNT/E. The infants recovered after treatment including botulism immune globulin intravenous (BIG-IV). C. butyricum BoNT/E was isolated from water from tanks housing pet 'yellow-bellied' terrapins (Trachemys scripta scripta): in case A the terrapins were in the infant's home; in case B a relative fed the terrapin prior to holding and feeding the infant when both visited another relative. C. butyricum isolates from the infants and the respective terrapin tank waters were indistinguishable by molecular typing. Review of a case of C. butyricum BoNT/E botulism in the UK found that there was a pet terrapin where the infant was living. It is concluded that the C. butyricum-producing BoNT type E in these cases of infant botulism most likely originated from pet terrapins. These findings reinforce public health advice that reptiles, including terrapins, are not suitable pets for children aged <5 years, and highlight the importance of hand washing after handling these pets.
The workshop on animal botulism in Europe.
Skarin, Hanna; Tevell Åberg, Annica; Woudstra, Cédric; Hansen, Trine; Löfström, Charlotta; Koene, Miriam; Bano, Luca; Hedeland, Mikael; Anniballi, Fabrizio; De Medici, Dario; Olsson Engvall, Eva
2013-09-01
A workshop on animal botulism was held in Uppsala, Sweden, in June 2012. Its purpose was to explore the current status of the disease in Europe by gathering the European experts in animal botulism and to raise awareness of the disease among veterinarians and others involved in biopreparedness. Animal botulism is underreported and underdiagnosed, but an increasing number of reports, as well as the information gathered from this workshop, show that it is an emerging problem in Europe. The workshop was divided into 4 sessions: animal botulism in Europe, the bacteria behind the disease, detection and diagnostics, and European collaboration and surveillance. An electronic survey was conducted before the workshop to identify the 3 most needed discussion points, which were: prevention, preparedness and outbreak response; detection and diagnostics; and European collaboration and surveillance. The main conclusions drawn from these discussions were that there is an urgent need to replace the mouse bioassay for botulinum toxin detection with an in vitro test and that there is a need for a European network to function as a reference laboratory, which could also organize a European supply of botulinum antitoxin and vaccines. The foundation of such a network was discussed, and the proposals are presented here along with the outcome of discussions and a summary of the workshop itself.
Therapeutic management of botulism in dairy cattle
Pandian, S. Jegaveera; Subramanian, M.; Vijayakumar, G.; Balasubramaniam, G. A.; Sukumar, K.
2015-01-01
Aim: To report the successful recovery of few dairy cattle from botulism in response to a modified therapeutic strategy. Materials and Methods: Seventy four naturally-occurring clinical cases of bovine botulism encountered during the period of 2012-2014 which were confirmed by mouse lethality test became material for this study. Affected animals were made into three groups based on the treatment modifications made during the course of study. Results and Discussion: With the modified therapeutic regimen, 17 animals recovered after 7-10 days of treatment. Clinical recovery took 2-30 days. Animals which were not given intravenous fluid and calcium recovered uneventfully. Cattle which were already treated with intravenous fluids, calcium borogluconate, and antibiotics did not recover. They were either died or slaughtered for salvage. Conclusion: In cattle with botulism, administration of Vitamin AD3E and activated charcoal aid the clinical recovery. Besides, strictly avoiding anti-clostridial antibiotics, fluid therapy, and calcium therapy may facilitate the clinical recovery. Upon fluid administration, the pulmonary congestion existed in the ailing cattle might have worsened the anoxia. Administration of antibiotics like penicillin, aminoglycosides, and tetracyclines further worsen the neuronal paralysis by increasing the availability of botulinum neurotoxin. Cattle in early botulism have fair chances of recovery with the modified therapy. PMID:27047034
Shot by a Gun … Missed by a Provider.
Garcia, Eddie; Zaid, Abdul H; Calello, Diane P; McHugh, Lisa; Arzumanov, Grant; Asrar, Najaf; Sapin, Ari; Fless, Kristin G
2018-04-01
Botulism is a paralytic disease caused by the neurotoxin produced by Clostridium botulinum. The majority of cases are due to ingestion or injection drug use. Wound botulism from traumatic injury is exceedingly rare, with only one to two cases reported each year in the United States. A 27-year-old man presented to the Emergency Department with diplopia, dysphagia, and progressive weakness 10 days after sustaining a gunshot wound to his right lower leg. He had been evaluated for the same complaints at a different facility the day prior and was discharged. His wound appeared well-healing, but a high suspicion for wound botulism led to rapid consultation with the state Poison Control Center and the Centers for Disease Control and Prevention. The patient developed worsening respiratory insufficiency and required mechanical ventilation. Expeditious treatment with equine heptavalent botulinum antitoxin resulted in significant recovery of strength in 4 days. Serum toxin bioassay tested positive for botulinum neurotoxin type A. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Wound botulism now accounts for the majority of adult botulism in the United States. It should be considered in any patient with signs of neuromuscular disease and a recent injury, even if the wound appears uninfected. Published by Elsevier Inc.
The Nanotechnology Characterization Laboratory (NCL) is collaborating with the Army to develop a candidate vaccine against botulism. Under a collaboration agreement between the National Cancer Institute and the U.S. Army Medical Research Institute of
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2010-01-22
obligate approximately $2 billion to acquire countermeasures against anthrax, botulism , radiation, and smallpox. The HHS has also employed the...see “Acquisitions”). The HHS used these contracts to purchase treatments for botulism and internal radioactive particle contamination. See U.S
BOTULISM E IN LAKE ERIE: ECOLOGY AND LOWER FOOD WEB TRANSFER
This project will determine the environmental conditions that favor botulism Type E bacteria in Lake Erie and explore whether quagga mussels are altering bottom sediment conditions to favor C. botulinum growth. Analysis of environmental parameters, including water chemistry, alg...
Production of recombinant botulism antigens: a review of expression systems.
Moreira, G M S G; Cunha, C E P; Salvarani, F M; Gonçalves, L A; Pires, P S; Conceição, F R; Lobato, F C F
2014-08-01
Botulism is a paralytic disease caused by intoxication with neurotoxins produced by Clostridium botulinum. Despite their similar mechanism of action, the botulinum neurotoxins (BoNT) are classified in eight serotypes (A to H). As to veterinary medicine, the impact of this disease is essentially economic, since different species of production animals can be affected, especially by BoNT/C and D. In human health, botulism is feared in a possible biological warfare, what would involve mainly the BoNT/A, B, E and F. In both cases, the most effective way to deal with botulism is through prevention, which involves vaccination. However, the current vaccines against this disease have several drawbacks on their process of production and, besides this, can be dangerous to producers since it requires certain level of biosafety. This way, recombinant vaccines have been shown to be a great alternative for the development of vaccines against both animal and human botulism. All BoNTs have a 50-kDa light chain (LC) and a 100-kDa heavy chain (HC). The latter one presents two domains of 50 kDa, called the N-terminal (HN) and C-terminal (HC) halves. Among these regions, the HC alone seem to confer the proper immune response against intoxication. Since innumerous studies describe the expression of these distinct regions using different systems, strategies, and protocols, it is difficult to define the best option for a viable vaccine production. Thereby, the present review describes the problematic of botulism and discusses the main advances for the viable production of vaccines for both human and veterinary medicine using recombinant antigens. Copyright © 2014 Elsevier Ltd. All rights reserved.
Mazuet, Christelle; Legeay, Christine; Sautereau, Jean; Ma, Laurence; Bouchier, Christiane; Bouvet, Philippe; Popoff, Michel R.
2016-01-01
In France, human botulism is mainly food-borne intoxication, whereas infant botulism is rare. A total of 99 group I and II Clostridium botulinum strains including 59 type A (12 historical isolates [1947–1961], 43 from France [1986–2013], 3 from other countries, and 1 collection strain), 31 type B (3 historical, 23 recent isolates, 4 from other countries, and 1 collection strain), and 9 type E (5 historical, 3 isolates, and 1 collection strain) were investigated by botulinum locus gene sequencing and multilocus sequence typing analysis. Historical C. botulinum A strains mainly belonged to subtype A1 and sequence type (ST) 1, whereas recent strains exhibited a wide genetic diversity: subtype A1 in orfX or ha locus, A1(B), A1(F), A2, A2b2, A5(B2′) A5(B3′), as well as the recently identified A7 and A8 subtypes, and were distributed into 25 STs. Clostridium botulinum A1(B) was the most frequent subtype from food-borne botulism and food. Group I C. botulinum type B in France were mainly subtype B2 (14 out of 20 historical and recent strains) and were divided into 19 STs. Food-borne botulism resulting from ham consumption during the recent period was due to group II C. botulinum B4. Type E botulism is rare in France, 5 historical and 1 recent strains were subtype E3. A subtype E12 was recently identified from an unusual ham contamination. Clostridium botulinum strains from human botulism in France showed a wide genetic diversity and seems to result not from a single evolutionary lineage but from multiple and independent genetic rearrangements. PMID:27189984
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2010-06-23
obligate approximately $2 billion to acquire countermeasures against anthrax, botulism , radiation, and smallpox. The HHS has also employed the...BioShield funds described later in this report (see “Acquisitions”). The HHS used these contracts to purchase treatments for botulism and internal
Infantile botulism: a case report.
Lavoie, Danielle; Pawar, Gauri; Khan, Atiya
2006-01-01
Although rare, botulism should be a consideration in the differential diagnosis of hypotonia in children. The pattern of clinical presentation and physical examination should raise the suspicion to make the appropriate diagnosis. Prompt clinical diagnosis and immediate appropriate treatment reduce morbidity and/or mortality in this disease.
Foodborne Botulism in the United States, 1990–2000
Tucker, Nicole; Sulka, Alana; McLaughlin, Joseph; Maslanka, Susan
2004-01-01
Foodborne botulism, a potentially lethal neuroparalytic disease, is caused by ingesting preformed Clostridium botulinum neurotoxin. We reviewed surveillance data and reports from 1990 to 2000. Of 263 cases from 160 foodborne botulism events (episode of one or more related cases) in the United States, 103 (39%) cases and 58 events occurred in Alaska. Patients' median age was 48 years; 154 (59%) were female; the case-fatality rate was 4%. The median number of cases per event was 1 (range 1–17). Toxin type A caused 51% of all cases; toxin type E caused 90% of Alaska cases. A particular food was implicated in 126 (79%) events. In the lower 49 states, a noncommercial food item was implicated in 70 (91%) events, most commonly home-canned vegetables (44%). Two restaurant-associated outbreaks affected 25 persons. All Alaska cases were attributable to traditional Alaska Native foods. Botulism prevention efforts should be focused on those who preserve food at home, Alaska Natives, and restaurant workers. PMID:15498163
Docherty, Douglas E.; Franson, J. Christian; Brannian, Roger E.; Long, Renee R.; Radi, Craig A.; Krueger, David; Johnson, Robert F.
2012-01-01
In 1999, the U.S. Geological Survey (USGS) National Wildlife Health Center, Madison, Wisconsin, conducted a diagnostic investigation into a water bird mortality event involving intoxication with avian botulism type C and infection with avian chlamydiosis at the Benton Lake National Wildlife Refuge in Montana, USA. Of 24 carcasses necropsied, 11 had lesions consistent with avian chlamydiosis, including two that tested positive for infectious Chlamydophila psittaci, and 12 were positive for avian botulism type C. One bird tested positive for both avian botulism type C and C. psittaci. Of 61 apparently healthy water birds sampled and released, 13 had serologic evidence of C. psittaci infection and 7 were, at the time of capture, shedding infectious C. psittaci via the cloacal or oropharyngeal route. Since more routinely diagnosed disease conditions may mask avian chlamydiosis, these findings support the need for a comprehensive diagnostic investigation when determining the cause of a wildlife mortality event.
Sundeen, Grace; Barbieri, Joseph T
2017-09-02
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin.
Type C botulism in pelicans and other fish-eating birds at the Salton Sea
Rocke, T.E.; Nol, P.; Pelizza, C.; Sturm, K.K.
2004-01-01
In 1996, type C avian botulism killed over 10,000 pelicans and nearly 10,000 other fish-eating birds at the Salton Sea in southern California. Although botulism had been previously documented in waterbirds at the Sea, this die-off was unusual in that it involved primarily fish-eating birds. The American White Pelican (Pelecanus erythrorynchos) was the species with the greatest mortality in 1996. Since 1996, mortality has recurred every year but losses have declined (<2,000 birds/year), with relatively more Brown Pelicans (P. occidentalis) than White Pelicans afflicted. In 2000, morbidity and mortality of Brown Pelicans with type C botulism (1311) approached the numbers afflicted in 1996 (2034). In recent years, mortality reached a peak earlier in the summer, July and August, in contrast to 1996 when mortality reached a peak in September. An exotic fish species, tilapia (Oreochromis mossambicus), has been implicated as the source of toxin for birds at Salton Sea, but the source of toxin for fish is unknown.
Autopsy findings in botulinum toxin poisoning.
Devers, Kelly G; Nine, Jeffrey S
2010-11-01
In the United States, foodborne botulism is most commonly associated with home-canned food products. Between 1950 and 2005, 405 separate outbreaks of botulism were reported to the Centers for Disease Control and Prevention (CDC). Approximately 8% of these outbreaks were attributed to commercially produced canned food products. Overall, 5-10% of persons ingesting botulinum toxin die. Few reports exist pertaining to autopsy findings in cases of foodborne botulism. Here, we report the autopsy findings of a man who died after a prolonged illness caused by botulinum toxin exposure likely attributable to a commercially prepared food source. Despite extensive testing, our histopathologic findings were nonspecific. We therefore conclude that the forensic pathologist must become familiar with the neurotoxicity syndrome associated with this illness. Maintaining vigilance for botulism by carefully reviewing the decedent's clinical history will aid in the early identification and control of outbreaks, either foodborne or terrorism-related. 2010 American Academy of Forensic Sciences. Published 2010. This article is a U.S. Government work and is in the public domain in the U.S.A.
Sundeen, Grace; Barbieri, Joseph T.
2017-01-01
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin. PMID:28869493
Potulska-Chromik, Anna; Zakrzewska-Pniewska, Beata; Szmidt-Sałkowska, Elżbieta; Lewandowski, Jacek; Siński, Maciej; Przyjałkowski, Witold; Kostera-Pruszczyk, Anna
2013-10-30
Botulism is an acute form of poisoning caused by one of four types (A, B, E, F) toxins produced by Clostridium botulinum, ananaerobic, spore forming bacillus. Usually diagnosis of botulism is considered in patients with predominant motor symptoms: muscle weakness with intact sensation and preserved mental function. We report a case of 56-year-old Caucasian female with a history of arterial hypertension, who presented with acute respiratory failure and bilateral ptosis misdiagnosed as brainstem ischemia. She had severe external and internal ophtalmoplegia, and autonomic dysfunction with neither motor nor sensory symptoms from upper and lower limbs. Diagnosis of botulinum toxin poisoning was made and confirmed by serum antibody testing in the mouse inoculation test. Ophtalmoplegia, autonomic dysfunction and respiratory failure can be caused by botulism. Early treatment and intensive care is essential for survival and recovery. The electrophysiological tests are crucial to correct and rapid diagnosis. Botulism (especially type B) should be considered in any case of acute or predominant isolated autonomic dysfunction.
Suspected botulism in dairy cows and its implications for the safety of human food.
Cobb, S P; Hogg, R A; Challoner, D J; Brett, M M; Livesey, C T; Sharpe, R T; Jones, T O
2002-01-05
A large outbreak of suspected botulism occurred on a dairy farm. The affected animals were listless and showed signs ranging from hindlimb unsteadiness to lateral recumbency, although the most common presentation was sternal recumbency with an apparent hindlimb weakness when stimulated to rise. Postmortem examinations revealed no conclusive gross pathology or histopathology. The affected cattle were found to have neutrophilia and hyperglycaemia with no other consistent haematological or biochemical abnormalities. The combination of clinical signs, disease epidemiology and the ruling out of other differential diagnoses strongly supported a diagnosis of unconfirmed botulism; however, the source of toxin was not demonstrated. Botulism is a severe disease in human beings and there are uncertainties about the pharmacokinetics and pharmacodynamics of Clostridium botulinum toxins. In such circumstances, a precautionary approach to food safety is essential. Restrictions were placed on the movement of livestock and sale of milk from the farm premises until 14 days after the onset of the last clinical case.
Morris, J G; Snyder, J D; Wilson, R; Feldman, R A
1983-01-01
Data were obtained for the 96 hospitalized cases of infant botulism reported to the Centers for Disease Control between 1976-1980 from all states other than California. Forty-one cases were associated with Clostridium botulinum type A, 53 with type B, one with type F, and one with a strain of C. botulinum capable of producing both type B and F toxin. Cases occurred in 25 states; the disease was more common in the western part of the United States, with the highest attack rates reported for Utah and New Mexico. Birth-weights of hospitalized infants with infant botulism tended to be high compared with birth-weights in the United States population. Mothers of infants with infant botulism tended to be older and better educated than mothers in the general population. Seventy per cent of infants had been predominantly breast-fed; breast-feeding in type B cases was associated with a significantly older age at onset of illness. Images FIGURE 2 PMID:6638233
Staphylococcal food poisoning and botulism
Gilbert, R. J.
1974-01-01
Staphylococcal food poisoning and botulism are caused by the ingestion of food containing exotoxins. Outbreaks of both are still a problem in many countries. This paper attempts to summarize information relating to these illnesses, together with advice on how their incidence may be reduced, or better still prevented. PMID:4619651
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2011-03-03
anthrax, botulism , radiation, and smallpox. The HHS has also employed the emergency use authority several times, including during the 2009 H1N1 influenza...report (see “Acquisitions”). The HHS used these contracts to purchase treatments for botulism and internal radioactive particle contamination. See U.S
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2011-04-22
against anthrax, botulism , radiation, and smallpox. The HHS has also employed the emergency use authority several times, including during the 2009 H1N1...described later in this report (see “Acquisitions”). The HHS used these contracts to purchase treatments for botulism and internal radioactive particle
Mase, Sundari R.; Cole, Barbara; Stiles, John; Rosenberg, Jon; Velasquez, Linda; Radner, Allen; Inami, Greg
2009-01-01
Foodborne botulism occurred among inmates at 2 prisons in California in 2004 and 2005. In the first outbreak, 4 inmates were hospitalized, 2 of whom required intubation. In the second event, 1 inmate required intubation. Pruno, an alcoholic drink made illicitly in prisons, was the novel vehicle for these cases. PMID:19116055
Project BioShield: Authorities, Appropriations, Acquisitions, and Issues for Congress
2011-02-07
botulism , radiation, and smallpox. The HHS has also employed the emergency use authority several times, including to allow young children with H1N1...using Project BioShield funds described later in this report (see “Acquisitions”). The HHS used these contracts to purchase treatments for botulism and
Uriarte, Ane; Thibaud, Jean-Laurent; Blot, Stéphane
2010-01-01
Two dogs from the same owner were referred for ascending weakness and paresis of 2 to 3 days duration. Electromyography and electroneurography determined that there were normal F-waves, decreased compound action potential, and decreased activity on repetitive nerve stimulation. These findings were valuable in diagnosing botulism in the dogs. PMID:21197207
[Familiar outbreak of botulism at Ceará state, Brazil: case report].
Barboza, Morgana Maria de Oliveira; Santos, Norival Ferreira dos; Sousa, Oscarina Viana de
2011-01-01
Report of a family outbreak of botulism food poisoning involving a death, where gaps in the completion of medical records were identified. The study aimed to describe the pathology and emphasize to health professionals the need to provide adequate information relevant to epidemiological investigation of compulsory notification diseases.
The hazards of honey: infantile botulism
Smith, Jennifer K; Burns, Sarah; Cunningham, Steve; Freeman, Julie; McLellan, Ailsa; McWilliam, Kenneth
2010-01-01
Infantile botulism is a rare cause of neuromuscular weakness resulting from ingestion of Clostridium botulinum—an anaerobic Gram-positive bacillus found universally in soil. The only definite food source known to cause infantile botulism is honey; previously, links to formula milk have been postulated but not definitely sourced. We present an interesting case report of a 2-month-old infant with this rare condition, including the diagnostic difficulties that ensued. A brief overview of the condition follows. This is the first case in the UK in which C botulinum was successfully isolated from both the patient and the suspected source—a jar of honey. The importance of food labelling as a public health message is highlighted. PMID:22778374
Barrett, D. H.; Eisenberg, M. S.; Bender, T. R.; Burks, J. M.; Hatheway, C. L.; Dowell, V. R.
1977-01-01
Botulism outbreaks shown to be due to type A and type B toxin occurred in Alaska, a region previously known for only type E botulism. The outbreak due to type A toxin involved three people, two of whom died. The outbreak due to type B toxin involved nine people, none of whom died. Both outbreaks were in Inuit villages, and native foods were incriminated. The occurrence of these outbreaks strongly suggests that Clostridium botulinum, types A and B are indigenous to Alaska. The outbreaks underscore the need for initial treatment of patients with antitoxin that is trivalent (ABE), even in Arctic regions. PMID:332309
[Botulism, a clinical diagnosis].
Delbos, Valérie; Abgueguen, Pierre; Fanello, Serge; Brenet, Olivier; Alquier, Philippe; Granry, Jean-Claude; Pichard, Eric
2005-03-26
Foodborne botulism results from the effect of a neurotoxin produced by a sporulated anaerobic bacillus called Clostridium botulinum. The mode of contamination occurs through the consumption of foodstuff, already contaminated by the neurotoxin. Following an incubation period that varies from 2 hours to 8 days, the symptoms start with intestinal problems. Then paralysis of the cranial nerve pairs sets in, classically manifested by diplopia, dysphagia, dysphonia, areactive mydriasis and ptosis. The onset of motor disorders occurs in descending order with possible involvement of the respiratory muscles, hence requiring reanimation measures and sometimes mechanical ventilation. The diagnosis of botulism is clinical. Identification of the botulinum toxin in the blood or faeces of the patients or in the contaminating food stuff confirms the diagnosis.
Botulism-like syndrome after injections of botulinum toxin.
Cobb, D B; Watson, W A; Fernandez, M C
2000-06-01
Botulinum type A toxin (BTA) is an orphan drug used to treat several disorders of muscle spasticity. We report the first known case of systemic botulism-like syndrome induced by BTA therapy which resulted in respiratory arrest. Clinicians should be aware that systemic effects may occur with localized BTA therapy and may be life-threatening.
Evaluation of fluorescent-antibody tests as a means of confirming infant botulism.
Glasby, C; Hatheway, C L
1984-01-01
Fluorescent-antibody techniques were evaluated for confirming infant botulism. Seventy-seven stool specimens from suspected cases were examined. All 34 specimens containing viable Clostridium botulinum at time of study gave positive results (29 on direct smears and 34 on enrichments). Two false-positive reactions were observed. Images PMID:6394626
USDA-ARS?s Scientific Manuscript database
Current methods for detecting the presence of botulinum neurotoxins in food and other biological samples Botulinum neurotoxins (BoNTs), the causative agents of botulism, are among the most lethal human bacterial toxins and the causative agent of botulism. BoNTs are also classified as Select Agents ...
Cluster of botulism among Dutch tourists in Turkey, June 2008.
Swaan, C M; van Ouwerkerk, I M; Roest, H J
2010-04-08
In June 2008, three Dutch tourists participating in a mini-cruise in Turkey needed urgent repatriation for antitoxin treatment because of symptoms of botulism. Because there was a shortage of antitoxin in the Netherlands, an emergency delivery was requested from the manufacturer in Germany. An outbreak investigation was initiated into all nine cruise members, eight of whom developed symptoms. C. botulinum type B was isolated in stool culture from four of them. No other patients were notified locally. Food histories revealed locally purchased unprocessed black olives, consumed on board of the ship, as most likely source, but no left-overs were available for investigation. C. botulinum type D was detected in locally purchased canned peas, and whilst type D is not known to be a cause of human intoxication, its presence in a canned food product indicates an inadequate preserving process. With increasing tourism to areas where food-borne botulism is reported regularly special requests for botulism antitoxin may become necessary. Preparing an inventory of available reserve stock in Europe would appear to be a necessary and valuable undertaking.
The First Case(s) of Botulism in Vienna in 21 Years: A Case Report.
Vossen, Matthias Gerhard; Gattringer, Klaus-Bernhard; Wenisch, Judith; Khalifeh, Neda; Koreny, Maria; Spertini, Verena; Allerberger, Franz; Graninger, Wolfgang; Kornschober, Christian; Lagler, Heimo; Reitner, Andreas; Sycha, Thomas; Thalhammer, Florian
2012-01-01
We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. We review the available literature, the compiled clinical data, and observations. After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production.
The First Case(s) of Botulism in Vienna in 21 Years: A Case Report
Vossen, Matthias Gerhard; Gattringer, Klaus-Bernhard; Wenisch, Judith; Khalifeh, Neda; Koreny, Maria; Spertini, Verena; Allerberger, Franz; Graninger, Wolfgang; Kornschober, Christian; Lagler, Heimo; Reitner, Andreas; Sycha, Thomas; Thalhammer, Florian
2012-01-01
We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. Methods: We review the available literature, the compiled clinical data, and observations. Results: After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. Conclusion: Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production. PMID:22779015
Vaccination of cattle with a recombinant bivalent toxoid against botulism serotypes C and D.
Cunha, Carlos E P; Moreira, Gustavo M S G; Salvarani, Felipe M; Neves, Monique S; Lobato, Francisco C F; Dellagostin, Odir A; Conceição, Fabricio R
2014-01-03
Cattle botulism is a fatal intoxication caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D resulting in economic losses. Vaccination is the most effective way to control botulism. However, the commercially available vaccines are difficult and hazardous to produce. Neutralizing antibodies against the C-terminal fragment of the BoNT heavy chain (HC) are known to protect against lethal doses of BoNTs. We report the vaccination of cattle with a previously tested recombinant chimera consisting of Escherichia coli heat-labile enterotoxin B subunit and the HC of BoNTs C and D. Vaccinated animals produced neutralizing antibodies against serotypes C and D averaging 5±0 and 6.14±1.06IU/mL, respectively. For BoNT D, the titers were greater than those measured for the commercial vaccine, which induced titers of 5±0 and 2.85±1.35 against the respective serotypes, suggesting that this chimera is effective against cattle botulism. Copyright © 2013 Elsevier Ltd. All rights reserved.
Relun, A; Dorso, L; Douart, A; Chartier, C; Guatteo, R; Mazuet, C; Popoff, M R; Assié, S
2017-12-01
Type D bovine botulism outbreaks associated with poultry litter are increasingly reported in European countries, but the circumstances of exposure to Clostridium botulinum toxins remain unclear. In spring 2015, a large type D/C bovine botulism outbreak affected a farm with dairy and poultry operations. Epidemiological and laboratory investigations strongly suggest that the outbreak was caused by feeding cattle with insufficiently acidified grass silage that was contaminated by type D/C C. botulinum spores. The source of the spores remains unclear, but could have been a stack of poultry litter stored in the grass silage pasture before harvesting. The presence of putrefied poultry carcasses mixed in with the litter is relatively unlikely considering the careful daily removal of poultry carcasses. These findings reinforce the importance of proper ensiling of feed materials and highlight the need for safe disposal of poultry litter, even in the case of good management of poultry deadstock, in order to prevent bovine botulism.
Souillard, R; Le Maréchal, C; Hollebecque, F; Rouxel, S; Barbé, A; Houard, E; Léon, D; Poëzévara, T; Fach, P; Woudstra, C; Mahé, F; Chemaly, M; Le Bouquin, S
2015-10-22
Ten cattle farms located in an area with a recent history of poultry botulism outbreaks were investigated to evaluate the occurrence of toxigenic C. botulinum in healthy cattle. Environmental samples in the 10 cattle farms and bovine fecal contents in farms with a confirmed environmental contamination were collected. Detection of C. botulinum toxin genes C, D, C/D, D/C and E was performed using real-time PCR. 4.9% (7/143) of the environmental samples collected in the 10 investigated cattle farms were positive for C. botulinum type C/D. Theses samples (boot-swabs in stalls and on pasture and water of a stream) were collected in 3 different farms. One cow dung sample and 3 out of 64 fecal contents samples collected in a single farm were also positive for C. botulinum type C/D. This study demonstrates that cattle are probably indirectly contaminated via poultry botulism in the area and that they can be intermittent carrier of C. botulinum type C/D after poultry botulism outbreaks in mixed farms. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Liu, Jing; Gao, Shan; Kang, Lin; Ji, Bin; Xin, Wenwen; Kang, Jingjing; Li, Ping; Gao, Jie; Wang, Hanbin; Wang, Jinglin; Yang, Hao
2017-03-01
Botulism is a severe and potentially lethal paralytic disease caused by several botulinum neurotoxin-producing Clostridia spp. In China, the majority of the cases caused by botulism were from less-developed rural areas. Here, we designed specific substrate peptides and reconfigured gold nanoparticle-based lateral flow test strip (LFTS) to develop an endopeptidase-based lateral flow assay for the diagnosis of botulism. We performed this lateral flow assay on botulinum neurotoxin-spiked human serum samples. The as-prepared LFTS had excellent performance in the detection of botulinum neurotoxin using only 1 μL of simulated serum, and its sensitivity and specificity were comparable to that of mouse lethality assay. Moreover, the assay takes only half a day and does not require highly trained laboratory staff, specialized facility, or equipment. Finally, our LFTS can be potentially extended to other serotypes of BoNTs by designing specific substrate peptides against the different types of BoNTs. Overall, we demonstrate a strategy by which LFTS and endopeptidase activity assays can be integrated to achieve facile and economic diagnosis of botulism in resource-limited settings.
Juliao, Patricia C; Maslanka, Susan; Dykes, Janet; Gaul, Linda; Bagdure, Satish; Granzow-Kibiger, Lynae; Salehi, Ellen; Zink, Donald; Neligan, Robert P; Barton-Behravesh, Casey; Lúquez, Carolina; Biggerstaff, Matthew; Lynch, Michael; Olson, Christine; Williams, Ian; Barzilay, Ezra J
2013-02-01
On 7 and 11 July 2007, health officials in Texas and Indiana, respectively, reported 4 possible cases of type A foodborne botulism to the US Centers for Disease Control and Prevention. Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin. Investigators reviewed patients' medical charts and food histories. Clinical specimens and food samples were tested for botulinum toxin and neurotoxin-producing Clostridium species. Investigators conducted inspections of the cannery that produced the implicated product. Eight confirmed outbreak associated cases were identified from Indiana (n = 2), Texas (n = 3), and Ohio (n = 3). Botulinum toxin type A was identified in leftover chili sauce consumed by the Indiana patients and 1 of the Ohio patients. Cannery inspectors found violations of federal canned-food regulations that could have led to survival of Clostridium botulinum spores during sterilization. The company recalled 39 million cans of chili. Following the outbreak, the US Food and Drug Administration inspected other canneries with similar canning systems and issued warnings to the industry about the danger of C. botulinum and the importance of compliance with canned food manufacturing regulations. Commercially produced hot dog chili sauce caused these cases of type A botulism. This is the first US foodborne botulism outbreak involving a commercial cannery in >30 years. Sharing of epidemiologic and laboratory findings allowed for the rapid identification of implicated food items and swift removal of potentially deadly products from the market by US food regulatory authorities.
Mazuet, Christelle; Legeay, Christine; Sautereau, Jean; Ma, Laurence; Bouchier, Christiane; Bouvet, Philippe; Popoff, Michel R
2016-06-13
In France, human botulism is mainly food-borne intoxication, whereas infant botulism is rare. A total of 99 group I and II Clostridium botulinum strains including 59 type A (12 historical isolates [1947-1961], 43 from France [1986-2013], 3 from other countries, and 1 collection strain), 31 type B (3 historical, 23 recent isolates, 4 from other countries, and 1 collection strain), and 9 type E (5 historical, 3 isolates, and 1 collection strain) were investigated by botulinum locus gene sequencing and multilocus sequence typing analysis. Historical C. botulinum A strains mainly belonged to subtype A1 and sequence type (ST) 1, whereas recent strains exhibited a wide genetic diversity: subtype A1 in orfX or ha locus, A1(B), A1(F), A2, A2b2, A5(B2') A5(B3'), as well as the recently identified A7 and A8 subtypes, and were distributed into 25 STs. Clostridium botulinum A1(B) was the most frequent subtype from food-borne botulism and food. Group I C. botulinum type B in France were mainly subtype B2 (14 out of 20 historical and recent strains) and were divided into 19 STs. Food-borne botulism resulting from ham consumption during the recent period was due to group II C. botulinum B4. Type E botulism is rare in France, 5 historical and 1 recent strains were subtype E3. A subtype E12 was recently identified from an unusual ham contamination. Clostridium botulinum strains from human botulism in France showed a wide genetic diversity and seems to result not from a single evolutionary lineage but from multiple and independent genetic rearrangements. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Examination of feces and serum for diagnosis of infant botulism in 336 patients.
Hatheway, C L; McCroskey, L M
1987-01-01
In the 12-year period 1975 to 1987, feces from 336 infants were examined for botulinal neurotoxin and Clostridium botulinum. All the infants had illnesses which prompted their physicians to consider infant botulism in the diagnosis. Stool specimens from 113 of the infants yielded organisms that produced botulinal neurotoxins assumed to be responsible for the illness. The types of botulinal toxin in the confirmed cases were distributed as follows: 38 A, 69 B, 2 atypical B, 1 E, 1 F, 1 A + B, and 1 B + F. The type A and B toxins in a single infant were produced by two different strains of organism, and the type B and F toxins in another infant were produced by a single strain. The physiological characteristics of all the isolated toxigenic organisms except two were consistent with those of group I (proteolytic) C. botulinum. The toxigenic isolate from the infant with type E botulism was identified as C. butyricum, and that from the infant with type F botulism was identified as C. barati. Toxin of the same type as produced by the isolated organisms was identified in feces of 98 of 111 culture-positive infants. Botulinal toxin was identified in the serum of 9 of 67 culture-positive infants (8 of 22 infants with type A organisms; 1 of 43 infants with type B organisms; neither of 2 infants with A + B or atypical type B organisms). Botulinal toxin was not detected in feces (206 infants) or in serum (114 infants) of the culture-negative infants. The culture-positive infants had clinical features and a course of illness consistent with those of infant botulism. Most of the culture-negative infants probably had illnesses other than botulism, but specimens might have been obtained late in some infants' illnesses, when the organism had disappeared. PMID:3323228
Tarkhashvili, N; Chokheli, M; Chubinidze, M; Abazashvili, N; Chakvetadze, N; Imnadze, P; Kretsinger, K; Varma, J; Sobel, J
2015-04-01
Foodborne botulism is a severe, paralytic illness caused by ingestion of preformed neurotoxins produced by Clostridium botulinum. In 2003, we conducted a population-based household survey of home canning practices to explore marked regional variations in botulism incidence in the Republic of Georgia (ROG). We designed a cluster sampling scheme and subdivided each of the 10 regions of the ROG into a variable number of strata. Households were selected from each stratum using a two-step cluster sampling methodology. We administered a questionnaire about home canning practices to household members responsible for food preparation. Using multivariate logistic regression analysis, we modeled high (eastern ROG) against low (western ROG) incidence areas. Overall, we surveyed 2,742 households nationwide. Home canning with a capping device hermetically sealing the lid covering the jar was practiced by 1,909 households (65.9%; 95% confidence interval [CI]: 59.8 to 72.1%). Canning was more prevalent in regions of low botulism incidence (34 versus 32%; P < 0.01). When compared with low-botulism areas, the following practices were associated with an increased risk in high-botulism areas: ≥ 6 months between canning vegetables and consuming them (adjusted odds ratio [aOR] = 2.1; 95% CI: 1.3 to 3.5) and adding any of the following ingredients to the jar at time of preparation: >1 tablespoon of salt per liter (aOR = 5.1; 95% CI: 1.2 to 22.6); vinegar (aOR = 2.2; 95% CI: 1.3 to 3.7), and greens (aOR = 5.6; 95% CI: 1.7 to 18.2). The following practices were associated with a decreased risk in high-botulism areas: >57 jars canned per household annually (aOR = 0.5; 95% CI: 0.3 to 0.9), covering or immersing vegetables in boiling water before placing them into the jar (aOR = 0.3 95% CI: 0.2 to 0.6), covering or immersing vegetables in boiling water after placing them into the jar (aOR = 0.4; 95% CI: 0.2 to 0.9), or adding garlic (aOR = 0.2; 95% CI: 0.1 to 0.5) or aspirin (aOR = 0.1; 95% CI: 0.1 to 0.2) to the jar at the time of preparation.
TARKHASHVILI, N.; CHOKHELI, M.; CHUBINIDZE, M.; ABAZASHVILI, N.; CHAKVETADZE, N.; IMNADZE, P.; KRETSINGER, K.; VARMA, J.; SOBEL, J.
2015-01-01
Foodborne botulism is a severe, paralytic illness caused by ingestion of preformed neurotoxins produced by Clostridium botulinum. In 2003, we conducted a population-based household survey of home canning practices to explore marked regional variations in botulism incidence in the Republic of Georgia (ROG). We designed a cluster sampling scheme and subdivided each of the 10 regions of the ROG into a variable number of strata. Households were selected from each stratum using a two-step cluster sampling methodology. We administered a questionnaire about home canning practices to household members responsible for food preparation. Using multivariate logistic regression analysis, we modeled high (eastern ROG) against low (western ROG) incidence areas. Overall, we surveyed 2,742 households nationwide. Home canning with a capping device hermetically sealing the lid covering the jar was practiced by 1,909 households (65.9%; 95% confidence interval [CI]: 59.8 to 72.1%). Canning was more prevalent in regions of low botulism incidence (34 versus 32%; P < 0.01). When compared with low-botulism areas, the following practices were associated with an increased risk in high-botulism areas: ≥6 months between canning vegetables and consuming them (adjusted odds ratio [aOR] = 2.1; 95% CI: 1.3 to 3.5) and adding any of the following ingredients to the jar at time of preparation: >1 tablespoon of salt per liter (aOR = 5.1; 95% CI: 1.2 to 22.6); vinegar (aOR = 2.2; 95% CI: 1.3 to 3.7), and greens (aOR = 5.6; 95% CI: 1.7 to 18.2). The following practices were associated with a decreased risk in high-botulism areas: >57 jars canned per household annually (aOR = 0.5; 95% CI: 0.3 to 0.9), covering or immersing vegetables in boiling water before placing them into the jar (aOR = 0.3 95% CI: 0.2 to 0.6), covering or immersing vegetables in boiling water after placing them into the jar (aOR = 0.4; 95% CI: 0.2 to 0.9), or adding garlic (aOR = 0.2; 95% CI: 0.1 to 0.5) or aspirin (aOR = 0.1; 95% CI: 0.1 to 0.2) to the jar at the time of preparation. PMID:25836400
Wang, J F; Mao, X Y; Zhao, C
2014-01-01
The experiment were performed to investigate the poisoning-related proteins and main pathological changes after mouse suffered from injection of botulinum toxin serotype E. Dose of 0.75 LD50 botulinum toxin serotype E per mice were administrated by intraperitoneal injection. Survival mouse were picked as experimental group. The blood were collected from orbital blood and serum sample was separated by centrifugation. The heart, liver, spleen, lung, kidney were fixed in 10 % neutral buffered formalin and then developed paraffin sections. Serum protein components were analyzed by SDS-PAGE gel electrophoresis coupled with 2-DE SDS-PAGE gel electrophoresis. Differentially expressed proteins were analyzed by PDQUest8.0 software and subjected to ion trap mass spectrometry equipped with a high performance liquid chromatography system. The observation of pathological section showed that heart, liver, spleen, lung, kidney exhibited pathological changes in different degree, especially in heart, liver and lung tissues. Heart muscle tissue display serious inflammatory response, heart muscle fiber compulsively expanded and filled with erythrocyte and inflammatory exudates, some heart muscle fiber ruptured, even necrosis; hepatic cell in edge of liver occur apoptosis and some hepatic cell have disintegrated, and even died; pulmonary alveoli broken and partial vein filled with blood. Serum proteins component present a significant changes between control serum and botulism in 24 h by SDS-PAGE gel electrophoresis and 2-DE-SDS-PAGE gel electrophoresis. Twenty differentially expressed protein spots were observed in 2-DE profiles, in which 14 protein spots were undetectable in serum proteome under botulism, 3 protein spots exclusively expressed in state of botulism, 3 protein spots were low-expressed in serum proteome under botulism. Fourteen proteins have been identified among 20 spots elected on two-dimensional electrophoresis gels. Crystal proteins family exclusively expressed in control group serum. Haptoglobin were low-expressed under botulism in serum protein components, however, serum amyloid A only expressed in serum sample under botulism in 24 h, which were verified by Western-blot. Identified proteins involved in energy metabolism, cellular stress response, transcription, body defense and cell proliferation. These findings represent the first report of BoNT-induced changes in serum proteome and histopathology, and reinforce the utility of applying proteomic tools to the study of system-wide biological processes in normal and botulism.
Natural Clostridium botulinum Type C Toxicosis in a Group of Cats
Elad, D.; Yas-Natan, E.; Aroch, I.; Shamir, M. H.; Kleinbart, S.; Hadash, D.; Chaffer, M.; Greenberg, K.; Shlosberg, A.
2004-01-01
Clinical signs of botulism were observed in a group of eight cats, four of which died, after being fed pelican carrion. Clostridium botulinum type C was isolated from one cat. The microorganism and its toxin were found in the pelican. This is apparently the first report of natural botulism in cats. PMID:15528757
USDA-ARS?s Scientific Manuscript database
Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...
Badhey, H; Cleri, D J; D'Amato, R F; Vernaleo, J R; Veinni, V; Tessler, J; Wallman, A A; Mastellone, A J; Giuliani, M; Hochstein, L
1986-01-01
Type E botulism, one of the least common forms of botulinal intoxication on the East Coast of the United States, is described for two elderly patients with chronic underlying disease. Both patients consumed tainted kapchunka, a salted, ungutted whitefish. Gastrointestinal symptoms and signs were prominent, but neurologic complaints, although noted soon after the consumption of the fish in one patient, did not progress until late in the course of the patient's illness. One patient exhibited both urinary retention, which was reported mainly in one outbreak of type E botulism (M.G. Koenig, A. Spickard, M.A. Cardella, and D.E. Rogers, Medicine [Baltimore] 43:517-545, 1964), and muscular fasciculations, which have been rarely reported. PMID:3514662
Juliao, Patricia C.; Maslanka, Susan; Dykes, Janet; Gaul, Linda; Bagdure, Satish; Granzow-Kibiger, Lynae; Salehi, Ellen; Zink, Donald; Neligan, Robert P.; Barton-Behravesh, Casey; Lúquez, Carolina; Biggerstaff, Matthew; Lynch, Michael; Olson, Christine; Williams, Ian; Barzilay, Ezra J.
2015-01-01
Background On 7 and 11 July 2007, health officials in Texas and Indiana, respectively, reported 4 possible cases of type A foodborne botulism to the US Centers for Disease Control and Prevention. Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin. Methods Investigators reviewed patients’ medical charts and food histories. Clinical specimens and food samples were tested for botulinum toxin and neurotoxin-producing Clostridium species. Investigators conducted inspections of the cannery that produced the implicated product. Results Eight confirmed outbreak associated cases were identified from Indiana (n = 2), Texas (n = 3), and Ohio (n = 3). Botulinum toxin type A was identified in leftover chili sauce consumed by the Indiana patients and 1 of the Ohio patients. Cannery inspectors found violations of federal canned-food regulations that could have led to survival of Clostridium botulinum spores during sterilization. The company recalled 39 million cans of chili. Following the outbreak, the US Food and Drug Administration inspected other canneries with similar canning systems and issued warnings to the industry about the danger of C. botulinum and the importance of compliance with canned food manufacturing regulations. Conclusions Commercially produced hot dog chili sauce caused these cases of type A botulism. This is the first US foodborne botulism outbreak involving a commercial cannery in >30 years. Sharing of epidemiologic and laboratory findings allowed for the rapid identification of implicated food items and swift removal of potentially deadly products from the market by US food regulatory authorities. PMID:23097586
Pflug, Irving J
2010-05-01
The incidence of botulism in canned food in the last century is reviewed along with the background science; a few conclusions are reached based on analysis of published data. There are two primary aspects to botulism control: the design of an adequate process and the delivery of the adequate process to containers of food. The probability that the designed process will not be adequate to control Clostridium botulinum is very small, probably less than 1.0 x 10(-6), based on containers of food, whereas the failure of the operator of the processing equipment to deliver the specified process to containers of food may be of the order of 1 in 40, to 1 in 100, based on processing units (retort loads). In the commercial food canning industry, failure to deliver the process will probably be of the order of 1.0 x 10(-4) to 1.0 x 10(-6) when U.S. Food and Drug Administration (FDA) regulations are followed. Botulism incidents have occurred in food canning plants that have not followed the FDA regulations. It is possible but very rare to have botulism result from postprocessing contamination. It may thus be concluded that botulism incidents in canned food are primarily the result of human failure in the delivery of the designed or specified process to containers of food that, in turn, result in the survival, outgrowth, and toxin production of C. botulinum spores. Therefore, efforts in C. botulinum control should be concentrated on reducing human errors in the delivery of the specified process to containers of food.
Investigation of a type C/D botulism outbreak in free-range laying hens in France.
Souillard, R; Le Maréchal, C; Ballan, V; Rouxel, S; Léon, D; Balaine, L; Poëzevara, T; Houard, E; Robineau, B; Robinault, C; Chemaly, M; Le Bouquin, S
2017-04-01
In 2014, a botulism outbreak in a flock of laying hens was investigated in France. In the flock of 5020 hens, clinical signs of botulism occurred at 46 weeks of age. A type C/D botulism outbreak was confirmed using the mouse lethality assay for detection of botulinum toxin in serum and a real-time PCR test to detect Clostridium botulinum in intestinal contents. The disease lasted one week with a mortality rate of 2.6% without recurrence. Botulism in laying hens has rarely been reported. Five monthly visits were made to the farm between December 2014 and May 2015 for a longitudinal study of the persistence of C. botulinum in the poultry house after the outbreak, and to assess egg contamination by C. botulinum. Several samples were collected on each visit: in the house (from the ventilation circuit, the egg circuit, water and feed, droppings) and the surrounding area. Thirty clean and 30 dirty eggs were also swabbed at each visit. In addition, 12 dirty and 12 clean eggs were collected to analyse eggshell and egg content. The samples were analysed using real-time PCR to detect type C/D C. botulinum. The bacterium was still detected in the house more than 5 months after the outbreak, mostly on the walls and in the egg circuit. Regarding egg contamination, the bacteria were detected only on the shell but not in the content of the eggs. Control measures should therefore be implemented throughout the egg production period to avoid dissemination of the bacteria, particularly during egg collection.
Walton, Ryan N; Clemens, Alexander; Chung, Jackson; Moore, Stephen; Wharton, Deborah; Haydu, Liz; de Villa, Eileen; Sanders, Greg; Bussey, Jeff; Richardson, David; Austin, John W
2014-10-01
On April 17, 2012, two adult females presented to the hospital with symptoms of botulism. Patient A displayed shortness of breath, increasing lethargy, ptosis, and fixed and dilated pupils, and was intubated after admission. Patient B presented with shortness of breath, vomiting, and stridor. Both patients consumed a meal consisting of a traditionally prepared salted fish, fesikh, on the evening of April 16 during a gathering to celebrate Sham el-Nessim, an Egyptian holiday marking the beginning of spring. Foodborne botulism was suspected based on symptoms and consumption of potentially hazardous food. Antitoxin was administered to both patients on April 18. Another attendee of the Sham el-Nessim gathering (patient C), who also consumed the implicated food, developed symptoms consistent with botulism on April 18. Clinical specimens from all three symptomatic attendees tested positive for either Clostridium botulinum or type E botulinum neurotoxin. Fesikh remaining from the shared meal contained both type E botulinum neurotoxin and C. botulinum type E organisms. Unsold fesikh shad and fesikh sardines tested positive for C. botulinum type E, while unsold fesikh mullet pieces in oil tested positive for both C. botulinum type E and type E botulinum neurotoxin. After consultation with public health investigators, all fesikh products were voluntarily withheld from sale by the manufacturer prior to laboratory confirmation of contamination. Additional illnesses were likely prevented by these precautionary holds, which underscores the importance of timely public health action based on epidemiological evidence available in advance of laboratory results. This is the first documented outbreak of foodborne botulism associated with fesikh to occur in Canada.
Galldiks, Norbert; Nolden-Hoverath, Silke; Kosinski, Christoph M; Stegelmeyer, Ulrike; Schmidt, Sylvia; Dohmen, Christian; Kuhn, Jens; Gerbershagen, Kathrin; Bewermeyer, Heiko; Walger, Peter; Biniek, Rolf; Neveling, Michael; Jacobs, Andreas H; Haupt, Walter F
2007-01-01
Wound infections due to Clostridium botulinum in Germany are rare and occur predominantly in heroin injectors, especially after subcutaneous or intramuscular injection of heroin ("skin popping"), which is contaminated with spores of C. botulinum. We report a rapid geographical clustering of cases in Germany in a region between Cologne, Bonn, and Aachen with wound botulism and consecutive systemic C. botulinum intoxication in intravenous drug users (IDUs) within 6 weeks in October and November 2005. A group of 12 IDUs with wound botulism after "skin popping." Clinical data were available in 11 (92%) of 12 patients; in 7 (58%) of the 12 cases, there was cranial nerve involvement including mydriasis, diplopia, dysarthria, and dysphagia, followed by progressing symmetric and flaccid paralysis of proximal muscles of the neck, arms, trunk, and respiratory muscles. Mechanical respiratory support was necessary. Five of the IDUs were treated with antitoxin, but mechanical respiratory support could not be avoided. The mean ventilation duration was 27.4 days (range 6-77 days). In 4 patients (33%), mechanical ventilation could be avoided; two were treated with antitoxin. This report describes rapid geographical clustering of wound botulism with severe respiratory complications in IDUs after "skin popping," which has not previously been reported either in Germany or any other European country. Based on these observations and those in other European countries, we conclude that there is a trend towards "skin popping," suggesting a change in injection practices in IDUs. Secondly, we conclude that the total number of cases with wound botulism is likely to increase because "skin popping" is the main risk factor.
Mazuet, Christelle; Ezan, Eric; Volland, Hervé; Becher, François
2012-01-01
In two outbreaks of food-borne botulism in France, Clostridium botulinum type A was isolated and characterized from incriminated foods. Botulinum neurotoxin type A was detected in the patients' sera by mouse bioassay and in vitro endopeptidase assay with an immunocapture step and identification of the cleavage products by mass spectrometry. PMID:22993181
Laboratory Diagnostics of Botulism
Lindström, Miia; Korkeala, Hannu
2006-01-01
Botulism is a potentially lethal paralytic disease caused by botulinum neurotoxin. Human pathogenic neurotoxins of types A, B, E, and F are produced by a diverse group of anaerobic spore-forming bacteria, including Clostridium botulinum groups I and II, Clostridium butyricum, and Clostridium baratii. The routine laboratory diagnostics of botulism is based on the detection of botulinum neurotoxin in the patient. Detection of toxin-producing clostridia in the patient and/or the vehicle confirms the diagnosis. The neurotoxin detection is based on the mouse lethality assay. Sensitive and rapid in vitro assays have been developed, but they have not yet been appropriately validated on clinical and food matrices. Culture methods for C. botulinum are poorly developed, and efficient isolation and identification tools are lacking. Molecular techniques targeted to the neurotoxin genes are ideal for the detection and identification of C. botulinum, but they do not detect biologically active neurotoxin and should not be used alone. Apart from rapid diagnosis, the laboratory diagnostics of botulism should aim at increasing our understanding of the epidemiology and prevention of the disease. Therefore, the toxin-producing organisms should be routinely isolated from the patient and the vehicle. The physiological group and genetic traits of the isolates should be determined. PMID:16614251
Kongsaengdao, Subsai; Samintarapanya, Kanoksri; Rusmeechan, Siwarit; Sithinamsuwan, Pasiri; Tanprawate, Surat
2009-08-01
In this study we describe the electrophysiological findings in botulism patients with neuromuscular respiratory failure from major botulism outbreaks in Thailand. High-rate repetitive nerve stimulation testing (RNST) of the abductor digiti minimi (ADM) muscle of 17 botulism patients with neuromuscular respiratory failure showed mostly incremental responses, especially in response to >20-HZ stimulation. In the most severe stage of neuromuscular respiratory failure, RNST failed to elicit a compound muscle action potential (CMAP) of the ADM muscle. In the moderately severe stage, the initial CMAPs were of very low amplitude, and a 3-HZ RNST elicited incremental or decremental responses. A 10-HZ RNST elicited mainly decremental responses. In the early recovery stage, the initial CMAP amplitudes of the ADM muscle improved, with initially low amplitudes and an incremental response to 3- and 10-HZ RNSTs. Improved electrophysiological patterns of the ADM muscle correlated with improved respiratory muscle function. Incremental responses to 20-HZ RNST were most useful for diagnosis. The initial electrodiagnostic sign of recovery following treatment of neuromuscular respiratory failure was an increased CMAP amplitude and an incremental response to 10-20-HZ RNST. Muscle Nerve 40: 271-278, 2009.
[Familial occurrence of botulism - a case report].
AmbroŽová, Helena; DŽupová, Olga; Smíšková, Dita; Roháčová, Hana
2014-06-01
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.
Frozen, Fully-Cooked Products and Botulism--Food Safety Advisory
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Type B botulism associated with roasted eggplant in oil--Italy, 1993.
1995-01-20
In August and October 1993, public health officials in Italy were notified of seven cases of type B botulism from two apparently unrelated outbreaks in different communities. Investigations were initiated by the Regional Health Observatory of Campania and the Italian National Institute of Health. This report summarizes the outbreak investigations, which indicated that illness was associated with eating commercially prepared roasted eggplant in oil.
Krüger, Monika; Neuhaus, Jürgen; Herrenthey, Anke Große; Gökce, M Mourat; Schrödl, Wieland; Shehata, Awad A
2014-08-01
The aim of this study is to investigate Clostridium botulinum at a Saxony dairy farm with 159 cows and 18 heifers. The animals exhibited clinical symptoms of chronic botulism. To determine the source of the infection, feces, blood, organs, and gastrointestinal fluids of dead or euthanized cows; as well as soil, water, silage and manure were tested for C. botulinum spores and BoNTs using ELISA. BoNT/C and C. botulinum type C were detected in 53% and 3% of tested animals, respectively, while BoNT/D and C. botulinum type D were detected in 18% of the animals. C. botulinum also was detected in organs, gastrointestinal fluids, drinking water and manure. To evaluate possible treatments, animals were given Jerusalem artichoke syrup (JAS), Botulism vaccine (formalinised aluminum hydroxide gel adsorbed toxoid of C. botulinum types C and D) or a suspension of Enterococcus faecalis. After four weeks treatment with JAS, BoNT/C and C. botulinum type C were not detected in feces. In contrast, BoNT/D and C. botulinum type D were not significantly influenced by the JAS treatment. Vaccination with botulism vaccine and the E. faecalis suspension significantly decreased BoNT/D and C. botulinum type D. A significant increase of Enterococci was detected in animals treated with E. faecalis. Interestingly, there was a negative correlation between the detection of both BoNT and C. botulinum with the concentration of Enterococci in feces. Although C. botulinum C and D antibodies increased significantly (p < 0.0001) after vaccination with the botulism vaccine, the reduction of C. botulinum and BoNT in feces did not result in recovery of the animals because they were deficient of trace elements [manganese (Mn), cobalt (Co), copper (Cu) and selenium (Se)]. Animals treated with trace elements recovered. It appears that intestinal microbiota dysbiosis and trace element deficiency could explain the extensive emergence of chronic Botulism. Copyright © 2014 Elsevier Ltd. All rights reserved.
Foodborne botulism in southwest Romania during the post-communism period 1990-2007.
Neghina, Adriana Maria; Marincu, Iosif; Moldovan, Roxana; Iacobiciu, Ioan; Neghina, Raul
2010-02-01
This study was a retrospective investigation of botulism cases over a period of 18 years following major political and economic changes, addressing the question of whether this disease is still an important health concern in southwest Romania. The medical records of botulism cases were used as the source of data. Patients from five southwest Romanian counties were hospitalized at Victor Babes Hospital of Infectious Diseases in Timisoara during the period 1990-2007. The median annual incidence of botulism cases in southwest Romania decreased from 0.1 per 100 000 persons during 1990-1998, to 0.05 per 100 000 persons during 1999-2007. Most of the cases (18.6%) were diagnosed in 1990, immediately following the communism period. The median age of the patients was 38 years (range 16-73 years); 24 (55.8%) were male; the case fatality rate was 2.3%. A significantly higher incidence rate of 2.7 cases per 100 000 persons occurred in rural areas, even though most of the cases (53.5%) were inhabitants of urban areas. The clinical pattern included: difficulty swallowing (79.1%), double and/or blurred vision (69.8%), dry mouth (60.5%), drooping eyelids (51.2%), vomiting (39.5%), mydriasis (37.2%), constipation (27.9%), abdominal pain (23.3%), and slurred speech (18.6%). All cases were attributed to contaminated food sources, mainly home-prepared traditional pork products. Although the botulism cases decreased over the study period in southwest Romania, this life-threatening disease continues to be an important concern. A strategy addressing individual behaviors in the home is needed to improve food safety. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Caballero, P; Troncoso, M; Patterson, S I; López Gómez, C; Fernandez, R; Sosa, M A
2016-10-01
The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain. In addition, purified neurotoxins of both strains were found to be enriched in a band of 300 kDa, whereas the A-Hall strain was mainly made up of a band of ∼600 kDa. This finding is in line with the lack of hemagglutinating activity of the neurotoxins under study. Moreover, the proteolytic activity of C. botulinum neurotoxins was evaluated against SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins from rat brain. It was observed that both, SNAP 25 (synaptosomal-associated protein 25) and VAMP 2 (vesicle-associated membrane protein) were cleaved by the neurotoxins isolated from the soil strains, whereas the neurotoxins from infant botulism strains only induced a partial cleavage of VAMP 2. On the other hand, the neurotoxin from the A-Hall strain was able to cleave both proteins, though at a lesser extent. Our data indicate that the C.botulinum strain isolated from the soil, and its BoNT, exhibit different properties compared to the strain obtained from infant botulism patients, and from the A-Hall archetype. Copyright © 2016 Elsevier Ltd. All rights reserved.
Effective and rapid treatment of wound botulism, a case report.
Schulte, M; Hamsen, U; Schildhauer, T A; Ramczykowski, T
2017-10-26
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. 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. 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.
Emergency department identification and critical care management of a Utah prison botulism outbreak.
Williams, Benjamin T; Schlein, Sarah M; Caravati, E Martin; Ledyard, Holly; Fix, Megan L
2014-07-01
We report botulism poisoning at a state prison after ingestion of homemade wine (pruno). This is an observational case series with data collected retrospectively by chart review. All suspected exposures were referred to a single hospital in October 2011. Twelve prisoners consumed pruno, a homemade alcoholic beverage made from a mixture of ingredients in prison environments. Four drank pruno made without potato and did not develop botulism. Eight drank pruno made with potato, became symptomatic, and were hospitalized. Presenting symptoms included dysphagia, diplopia, dysarthria, and weakness. The median time to symptom onset was 54.5 hours (interquartile range [IQR] 49-88 hours) postingestion. All 8 patients received botulinum antitoxin a median of 12 hours post-emergency department admission (IQR 8.9-18.8 hours). Seven of 8 patients had positive stool samples for type A botulinum toxin. The 3 most severely affected patients had respiratory failure and were intubated 43, 64, and 68 hours postingestion. Their maximal inspiratory force values were -5, -15, and -30 cm H2O. Their forced vital capacity values were 0.91, 2.1, and 2.2 L, whereas the 5 nonintubated patients had median maximal inspiratory force of -60 cm H2O (IQR -60 to -55) and forced vital capacity of 4.5 L (IQR 3.7-4.9). Electromyography abnormalities were observed in 1 of the nonintubated and 2 of the intubated patients. A pruno-associated botulism outbreak resulted in respiratory failure and abnormal pulmonary parameters in the most affected patients. Electromyography abnormalities were observed in the majority of intubated patients. Potato in the pruno recipe was associated with botulism. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.
Gray, Timothy J.; Wang, Qinning; Ng, Jimmy; Hicks, Leanne; Nguyen, Trang; Yuen, Marion; Hill-Cawthorne, Grant A.; Sintchenko, Vitali
2015-01-01
Infant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links. Clostridium botulinum isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS). In silico multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne bont/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of C. botulinum that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that C. botulinum from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST. PMID:26109442
McCallum, Nadine; Gray, Timothy J; Wang, Qinning; Ng, Jimmy; Hicks, Leanne; Nguyen, Trang; Yuen, Marion; Hill-Cawthorne, Grant A; Sintchenko, Vitali
2015-09-01
Infant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links. Clostridium botulinum isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS). In silico multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne bont/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of C. botulinum that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that C. botulinum from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Foodborne botulism in Poland in 2014
Czerwiński, Michał; Czarkowski, Mirosław P; Kondej, Barbara
The aim of the study is to assess the epidemiology of foodborne botulism in Poland in 2014 compared to previous years. We reviewed (1) surveillance data published in the annual bulletin “Infectious diseases and poisonings in Poland in 2014” and in previous publications, and (2) unpublished data retrieved from botulism case reports for 2014 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. In 2014, a total of 29 foodborne botulism cases (including 17 laboratory confirmed) was reported; the annual incidence rate (0.08 per 100,000 population) increased slightly in comparison to previous year, but was similar to the median incidence for years 2008 to 2012. The highest incidence in the country was reported in Lubelskie province (0.33). Incidence in rural areas (0.09) was only slightly higher than the incidence in urban areas (0.06). Men, had more than 4 times higher incidence than women; the highest incidence rate (0.31) was observed among men in the age group of 20-24 years. Most cases were associated with consumption of different types of commercially canned meat. Home-made vegetable meat preserves were also a common vehicle. All cases were hospitalized. Two deaths related to the disease were reported. Since 2008, the epidemiological situation of foodborne botulism in the country remains stable with an average 30 cases per year and corresponding incidence rate of 0.08 per 100,000 population. However, in 2014 draws attention a significant number of cases with undetermined food vehicle and relatively high percentage of cases with no laboratory confirmation. Therefore, it is important to enhance epidemiological investigation as well as laboratory capacity for surveillance.
Genetic Characterization of Clostridium botulinum Associated with Type B Infant Botulism in Japan▿
Umeda, Kaoru; Seto, Yoshiyuki; Kohda, Tomoko; Mukamoto, Masafumi; Kozaki, Shunji
2009-01-01
The 15 proteolytic Clostridium botulinum type B strains, including 3 isolates associated with infant botulism in Japan, were genetically characterized by phylogenetic analysis of boNT/B gene sequences, genotyping, and determination of the boNT/B gene location by using pulsed-field gel electrophoresis (PFGE) for molecular epidemiological analysis of infant botulism in Japan. Strain Osaka05, isolated from a case in 2005, showed a unique boNT/B gene sequence and was considered to be a new BoNT/B subtype by phylogenetic analysis. Strain Osaka06, isolated from a case in 2006, was classified as the B2 subtype, the same as strain 111, isolated from a case in 1995. The five isolates associated with infant botulism in the United States were classified into the B1 subtype. Isolates from food samples in Japan were divided into the B1 and the B2 subtypes, although no relation with infant botulism was shown by PFGE genotyping. The results of PFGE and Southern blot hybridization with undigested DNA suggested that the boNT/B gene is located on large plasmids (approximately 150 kbp, 260 kbp, 275 kbp, or 280 kbp) in five strains belonging to three BoNT/B subtypes from various sources. The botulinum neurotoxin (BoNT) of Osaka05 was suggested to have an antigenicity different from the antigenicities of BoNT/B1 and BoNT/B2 by a sandwich enzyme-linked immunosorbent assay with the recombinant BoNT/B-C-terminal domain. We established a multiplex PCR assay for BoNT/B subtyping which will be useful for epidemiological studies of type B strains and the infectious diseases that they cause. PMID:19571018
Erbguth, Frank J
2004-03-01
Food-borne botulism probably has accompanied mankind since its beginning. However, we have only few historical sources and documents on food poisoning before the 19th century. Some ancient dietary laws and taboos may reflect some knowledge about the life-threatening consumption of poisoned food. One example of such a dietary taboo is the 10th century edict of Emperor Leo VI of Byzantium in which manufacturing of blood sausages was forbidden. Some ancient case reports on intoxications with Atropa belladonna probably described patients with food-borne botulism, because the combination of dilated pupils and fatal muscle paralysis cannot be attributed to an atropine intoxication. At the end of the 18th century, some well-documented outbreaks of "sausage poisoning" in Southern Germany, especially in Württemberg, prompted early systematic botulinum toxin research. The German poet and district medical officer Justinus Kerner (1786-1862) published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822. Kerner did not succeed in defining the suspected "biological poison" which he called "sausage poison" or "fatty poison." However, he developed the idea of a possible therapeutic use of the toxin. Eighty years after Kerner's work, in 1895, a botulism outbreak after a funeral dinner with smoked ham in the small Belgian village of Ellezelles led to the discovery of the pathogen Clostridium botulinum by Emile Pierre van Ermengem, Professor of bacteriology at the University of Ghent. The bacterium was so called because of its pathological association with the sausages (Latin word for sausage = "botulus") and not-as it was suggested-because of its shape. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz. Copyright 2004 Movement Disorder Society
[Botulinum toxin: from poison to drug. A historical review].
Kreyden, O P; Geiges, M L; Böni, R; Burg, G
2000-10-01
Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning. The first case of botulism is believed to have occurred in 1735. An epidemic in Southern Germany in 1793 claimed the death of over the half of those patients who had become ill through eating uncooked blood sausages. The term "pharmakon" is Greek and implicates that a drug originates from poison (potion, remedy). Theophrastus Bombast von Hohenheim known as Paracelsus (1493/94-1541) first described this duality with his dictum "alle ding sind gift und nichts on gift; alein die dosis macht das ein ding kein gift ist" (only the dose makes a remedy poisonous). In Baden-Württemberg in 1817, the poet and physician Dr. Justinus Christian Kerner described the symptoms of botulism, so that at this time botulism was also called Kerner disease. Until the turn of the century the reason for poisoning was not known. Van Ermengem succeeded in isolating the anaerobic bacterium causing botulism, but the specific mechanism of BTX was only established after the second World War. In the late seventies the ophthalmologist Dr. Alan Scott used BTX the first time in the treatment of strabismus. The drug was then used in the treatment of several muscle spasticities such as, for example, torticollis or hemifacial spasm. Only recently BTX has been successfully used for focal hyperhidrosis. We review the history of botulinum toxin from its discovery in the nineteenth century and the research into its effect in the middle of the 20th century up to its clinical use at the present time.
Adams, Laura E.; Yasmin, Seema; Briggs, Graham; Redden, Kore; Silvas, Suzanne; Anderson, Shoana; Weiss, Joli; Tsang, Clarisse A.; Henke, Evan; Francies, Jessica; Herrick, Kristen; Lira, Rosa; Livar, Eugene; Thompson, Gerald; Sunenshine, Rebecca; Robinson, Byron F.; Bisgard, Kristine M.; Komatsu, Kenneth K.
2017-01-01
During July to November 2012, two botulism outbreaks (12 cases total) occurred in one all-male prison; both were associated with illicitly brewed alcohol (pruno) consumption. Inmate surveys were conducted to evaluate and develop prevention and education strategies. Qualitative surveys with open-ended questions were performed among inmates from rooms where outbreaks occurred to learn about pruno consumption. Quantitative surveys assessed knowledge gained after the outbreaks and preferred information sources. For the quantitative surveys, 250 inmates were randomly selected by bed from across the correctional facility and 164 inmates were interviewed. Only 24% of inmates reported any botulism knowledge before the outbreaks and education outreach, whereas 73% reported knowledge after the outbreaks (p < .01). Preferred information sources included handouts/fliers (52%) and the prison television channel (32%). PMID:26285594
A report on the pathology of type A botulism.
Toyoda, H; Omata, K; Fukai, K; Akai, K
1980-05-01
An autopsy case of type A botulism, a sacrifice during the first outbreak in Japan, was presented. The patient exhibited typical neuromuscular symptoms and died on the 8th day from the onset of illness. Type A Clostridium botulinum was demonstrated from the stools and the toxin from the blood serum during the course of disease. The infection source of botulinus bacilli, however, was not clarified. The autopsy diagnoses were made as follows; 1) type A botulism, 2) bronchopneumonia, 3) respirator brain, 4) congestion, 5) hemorrhage in vagal nerve, myocardium and endometrium, 6) gastric erosion, 7) cloudy swelling of kidneys, 8) enterocolitis, 9) focal necrosis of liver and adrenals, 10) demyelination of cranial nerves, and 11) focal hyaline degeneration of striated and smooth muscles and myocardium. The botulinus toxin was confirmed from the samples of cardiac blood or autopsy.
Medical Surveillance Monthly Report. Volume 21, Number 6
2014-06-01
presentations of diarrhea and vomiting (e.g., botulism, brucellosis, hep- atitis A, trichinosis, and typhoid fever ). For the purposes of this report...norovirus, salmonellosis, shigellosis, trichinosis, and typhoid fever . Informa- tion on GI outbreaks that occurred dur- ing the surveillance period, but... Typhoid fever 8 5 1 . 2 Listeriosis 4 1 1 1 1 Cholera 3 3 . . . Vibrio parahaemolyticus 3 2 . 1 . Trichinosis 3 1 1 1 . Botulism 2 . 2 . . Cyclospora
Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
2016-08-26
Richmond, California, USA 5Bureau of Microbial Hazards , Health Canada, Ottawa, Ontario, Canada 6Istituto Zooprofilattico Sperimentale delle Venezie...monoclonal antibody-based immunoassay for detecting type B Clostridium botulinum toxin produced in pure culture and an inoculated model cured meat system...A3 Loch Maree duck paste/Scotland, 1922 ACA57525 A4 strain 657 infant botulism/Texas, 1976 ACQ51417 A5 H04402 065 wound botulism (heroin), 2004
Prevention and Treament of Botulism
2014-01-01
Rationale for Antitoxin Treatment Although in use for more than four decades, equine antitoxins are still the only postexposure products available for...levels ofBoNT in humans as a function of time ,, I 13 Prevention and Treatment of Botulism Table 13.1 Botulinum antitoxins Product Source Years used ...components, the seven antitoxin sera- types are blended into a heptavalent product and filled into single- use vials for in- travenous (i.v.) infusion. The
Anniballi, Fabrizio; Fiore, Alfonsina; Löfström, Charlotta; Skarin, Hanna; Auricchio, Bruna; Woudstra, Cédric; Bano, Luca; Segerman, Bo; Koene, Miriam; Båverud, Viveca; Hansen, Trine; Fach, Patrick; Tevell Aberg, Annica; Hedeland, Mikael; Olsson Engvall, Eva; De Medici, Dario
2013-09-01
Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded animals, and some fishes. The disease is caused by exposure to toxins produced by Clostridium botulinum and other botulinum toxin-producing clostridia. Botulism in animals represents a severe environmental and economic concern because of its high mortality rate. Moreover, meat or other products from affected animals entering the food chain may result in a public health problem. To this end, early diagnosis is crucial to define and apply appropriate veterinary public health measures. Clinical diagnosis is based on clinical findings eliminating other causes of neuromuscular disorders and on the absence of internal lesions observed during postmortem examination. Since clinical signs alone are often insufficient to make a definitive diagnosis, laboratory confirmation is required. Botulinum antitoxin administration and supportive therapies are used to treat sick animals. Once the diagnosis has been made, euthanasia is frequently advisable. Vaccine administration is subject to health authorities' permission, and it is restricted to a small number of animal species. Several measures can be adopted to prevent or minimize outbreaks. In this article we outline all phases of management of animal botulism outbreaks occurring in wet wild birds, poultry, cattle, horses, and fur farm animals.
Mazuet, C; Yoon, E-J; Boyer, S; Pignier, S; Blanc, T; Doehring, I; Meziane-Cherif, D; Dumant-Forest, C; Sautereau, J; Legeay, C; Bouvet, P; Bouchier, C; Quijano-Roy, S; Pestel-Caron, M; Courvalin, P; Popoff, M R
2016-07-01
The clinical course of a case of infant botulism was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and Clostridium botulinum in stools. A C. botulinum A2 strain resistant to penicillins and with heterogeneous resistance to metronidazole was isolated from stool samples up to 110 days after onset. Antibiotic susceptibility was tested by disc agar diffusion and MICs were determined by Etest. Whole genome sequencing allowed detection of a gene cluster composed of blaCBP for a novel penicillinase, blaI for a regulator, and blaR1 for a membrane-bound penicillin receptor in the chromosome of the C. botulinum isolate. The purified recombinant penicillinase was assayed. Resistance to β-lactams was in agreement with the kinetic parameters of the enzyme. In addition, the β-lactamase gene cluster was found in three C. botulinum genomes in databanks and in two of 62 genomes of our collection, all the strains belonging to group I C. botulinum. This is the first report of a C. botulinum isolate resistant to penicillins. This stresses the importance of antibiotic susceptibility testing for adequate therapy of botulism. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Two outbreaks of type C and type D botulism in sheep and goats in south Africa.
Van der Lugt, J J; De Wet, S C; Bastianello, S S; Kellerman, T S; Van Jaarsveld, L P
1995-06-01
Two outbreaks of botulism in sheep and goats are described; in one, 329 out of 900 sheep in a feedlot died within 9 d of the onset of the disease and in the other, 100 sheep and goats out of 330 succumbed over a period of about 3 weeks. Animals were found dead or died suddenly, without exhibiting clinical signs. Others stood with lowered heads and showed drooling of saliva or a stiff gait. Paresis and/or paralysis were frequent signs in the terminal stages of the disease. Gross lesions such as the accumulation of fluids in body cavities, pulmonary oedema, foam in the trachea, epicardial haemorrhages and congestion of the mucosa of the small intestine, suggestive of heart failure, were present in animals from both outbreaks. Botulism was confirmed via the mouse toxicity test, by the demonstration of Type C and Type D toxins in the feed and intestinal contents of sheep from the first outbreak and Type D toxin in intestinal contents of sheep from the second. The clinical signs and macropathology in the outbreaks of botulism in sheep and goats in South Africa may resemble "krimpsiekte" and cardiac glycoside and ionophore poisoning, as well as other conditions causing heart failure.
Early, Real-Time Medical Diagnosis of Botulism by Endopeptidase-Mass Spectrometry.
Rosen, Osnat; Feldberg, Liron; Gura, Sigalit; Brosh-Nissimov, Tal; Guri, Alex; Zimhony, Oren; Shapiro, Eli; Beth-Din, Adi; Stein, Dana; Ozeri, Eyal; Barnea, Ada; Turgeman, Amram; Ben David, Alon; Schwartz, Arieh; Elhanany, Eytan; Diamant, Eran; Yitzhaki, Shmuel; Zichel, Ran
2015-12-15
Botulinum toxin was detected in patient serum using Endopeptidase-mass-spectrometry assay, although all conventional tests provided negative results. Antitoxin was administered, resulting in patient improvement. Implementing this highly sensitive and rapid assay will improve preparedness for foodborne botulism and deliberate exposure. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
2011-01-01
Clostridium botulinum type A progenitor toxins . Infect Immun 64:1589–1594 Li L, Singh BR (1999) Structure -function relationship of clostridial...experimental design and demonstration of the validity of the targeted neurologic therapeutic delivery approach based on recombinant botulinum toxin ...Endocytosis Exocytosis Molecular trafficking Cell maturation Botulism Targeted therapeutic Background Botulinum neurotoxins (BoNTs) are produced by
Botulinum neurotoxin vaccines: Past history and recent developments.
Rusnak, Janice M; Smith, Leonard A
2009-12-01
Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.
Adams, Laura E; Yasmin, Seema; Briggs, Graham; Redden, Kore; Silvas, Suzanne; Anderson, Shoana; Weiss, Joli; Tsang, Clarisse A; Henke, Evan; Francies, Jessica; Herrick, Kristen; Lira, Rosa; Livar, Eugene; Thompson, Gerald; Sunenshine, Rebecca; Robinson, Byron F; Bisgard, Kristine M; Komatsu, Kenneth K
2015-10-01
During July to November 2012, two botulism outbreaks (12 cases total) occurred in one all-male prison; both were associated with illicitly brewed alcohol (pruno) consumption. Inmate surveys were conducted to evaluate and develop prevention and education strategies. Qualitative surveys with open-ended questions were performed among inmates from rooms where outbreaks occurred to learn about pruno consumption. Quantitative surveys assessed knowledge gained after the outbreaks and preferred information sources. For the quantitative surveys, 250 inmates were randomly selected by bed from across the correctional facility and 164 inmates were interviewed. Only 24% of inmates reported any botulism knowledge before the outbreaks and education outreach, whereas 73% reported knowledge after the outbreaks (p < .01). Preferred information sources included handouts/fliers (52%) and the prison television channel (32%). © The Author(s) 2015.
[Wound botulism in heroin addicts in Germany].
Kuhn, J; Gerbershagen, K; Schaumann, R; Langenberg, U; Rodloff, A C; Mueller, W; Hartmann-Klosterkoetter, U; Bewermeyer, H
2006-05-05
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. 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. 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. 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.
Cost of Irradiating Bacon and the Associated Energy Savings
1979-03-01
Irradiated Food(s) Consumers Irradiation Cost Analysis Energy Savings Stan 1 izatlon Consumer Acceptance Meat ~~~~~~~~~~~~~~~~~ ~ ô. ~ iii~- ) I I...eliminating nitrites in bacon would reduce or eliminate the formation of highly carcinogenic nitrosami~es, but would Increase the threatof botulism...Sterilized by Irradiation, bacon without nitrite does not contain nitrosamines and does not cause botulism. Consumer panel taste tests show no difference
Mechanisms of Toxin Production of Food Bacteria (Clostridium botulinum)
1983-12-01
and domestic birds such as broiler chickens and turkeys. Animal botulism (caused by types C and D) also occurs in differ- ent areas of the world... digestive system or a state of consti- pation, a sympton frequently observed in animal or human botulism. No other pathogenic conditions were observed. When... digestive tract and flesh of morbid fish. This outbreak resulted in losses of 260 000 yearling coho salmon out of an original population of 871 000
Type C botulism losses at Horicon National Wildlife Refuge, 1978
Windingstad, R.M.; Duncan, R.M.; Drieslein, R.L.
1980-01-01
Avian botulism was responsible for the death of over 6,000 waterfowl at Horicon National Wildlife Refuge in Wisconsin in 1978. The outbreak occurred in early fall on a flooded 250 hectare fallow agricultural area on the northeast end of the refuge. The species most severely affected was the green-winged teal (Anas carolinensis), which made up almost 45% of the total birds found. Carcass pick-up, mouse toxicity tests, and antitoxin injections of waterfowl are discussed.
Anza, Ibone; Taggart, Mark A.; Pérez-Ramírez, Elisa; Crespo, Elena; Hofle, Ursula; Mateo, Rafael
2013-01-01
Between 1978 and 2008, 13 avian botulism outbreaks were recorded in the wetlands of Mancha Húmeda (central Spain). These outbreaks caused the deaths of around 20,000 birds from over 50 species, including globally endangered white-headed ducks (Oxyura leucoceophala). Here, a significant association was found between the number of dead birds recorded in each botulism outbreak and the mean temperature in July (always >26°C). The presence of Clostridium botulinum type C/D in wetland sediments was detected by real-time PCR (quantitative PCR [qPCR]) in 5.8% of 207 samples collected between 2005 and 2008. Low concentrations of Cl− and high organic matter content in sediments were significantly associated with the presence of C. botulinum. Seventy-five digestive tracts of birds found dead during botulism outbreaks were analyzed; C. botulinum was present in 38.7% of them. The prevalence of C. botulinum was 18.2% (n = 22 pools) in aquatic invertebrates (Chironomidae and Corixidae families) and 33.3% (n = 18 pools) in necrophagous invertebrates (Sarcophagidae and Calliphoridae families), including two pools of adult necrophagous flies collected around bird carcasses. The presence of the bacteria in the adult fly form opens up new perspectives in the epidemiology of avian botulism, since these flies may be transporting C. botulinum from one carcass to another. PMID:23645197
[Botulism in infancy - survey of literature based on a case report].
Berkes, Andrea; Szegedi, István; Szikszay, Edit; Gulyás, Márta; Oláh, Eva
2007-06-17
The authors have drawn attention to a rare disease called infant botulism, which raises some difficulties with regard to differential diagnosis. In the case of the six-month-old infant portrayed, infant botulism and food-born botulism appeared together. As a result of the severity of the disease and due to its rapid course observed in the presented case as well, the diagnosis has to be raised relying on the accurate patient's history and on the clinical examination, then it should be confirmed by appropriate examinations. In relation to presenting a case, the authors examine the microbiological background of the disease, its symptomatology, its epidemiological characteristics, the appropriate methods of electrophysiological examination and laboratory analysis as recommended in current literature, together with the difficulties that arise in differential diagnosis and also the possibilities of treatment. They pay special attention to the particular characteristics of the infant form of the disease, to the difficulties of making a diagnosis due to the characteristics of the age group and also to the questions in relation to the guiding principles of therapy. The rapid and fatal process observed in the presented case warns us that serious complications can occur even when up-to-date therapy is used. Therefore, despite the improvement in prognosis we have to strive to prevent the disease by spreading the proper regulations of nutritional hygiene.
Fan, Kit-Ling; Wang, Yan-Li; Chu, Gary; Leung, Ling-Pong
2016-12-01
Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. Two female adult patients with clinical botulism after botulinum toxin type A injection are described. Both patients had received intramuscular injection of botulinum toxin type A in their calves at beauty shops for cosmetic reasons. They developed clinical botulism about 3 days postinjection. They presented late to the emergency department. Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom onset, respectively. Both patients showed clinical improvement after the antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may present to the emergency department with systemic effects of botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum antitoxin treatment was observed in two patients who were given the drug 7 and 9 days after the occurrence of symptoms of botulism after cosmetic injection of botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even if patients present late. Copyright © 2016 Elsevier Inc. All rights reserved.
Environmental conditions synchronize waterbird mortality events in the Great Lakes
Prince, Karine; Chipault, Jennifer G.; White, C. LeAnn; Zuckerberg, Benjamin
2018-01-01
Since the 1960s, periodic outbreaks of avian botulism type E have contributed to large-scale die-offs of thousands of waterbirds throughout the Great Lakes of the United States. In recent years, these events have become more common and widespread. Occurring during the summer and autumn months, the prevalence of these die-offs varies across years and is often associated with years of warmer lake temperatures and lower water levels. Little information exists on how environmental conditions mediate the spatial and temporal characteristics of mortality events.In 2010, a citizen science programme, Avian Monitoring for Botulism Lakeshore Events (AMBLE), was launched to enhance surveillance efforts and detect the appearance of beached waterbird carcasses associated with avian botulism type E outbreaks in northern Lake Michigan. Using these data, our goal was to quantify the within-year characteristics of mortality events for multiple species, and to test whether the synchrony of these events corresponded to fluctuations in two environmental factors suspected to be important in the spread of avian botulism: water temperature and the prevalence of green macroalgae.During two separate events of mass waterbird mortality, we found that the detection of bird carcasses was spatially synchronized at scales of c. 40 km. Notably, the extent of this spatial synchrony in avian mortality matched that of fluctuations in lake surface water temperatures and the prevalence of green macroalgae.Synthesis and applications. Our findings are suggestive of a synchronizing effect where warmer lake temperatures and the appearance of macroalgae mediate the characteristics of avian mortality. In future years, rising lake temperatures and a higher propensity of algal masses could lead to increases in the magnitude and synchronization of avian mortality due to botulism. We advocate that citizen-based monitoring efforts are critical for identifying the potential environmental conditions associated with widespread mortality events and estimating future risk to waterbird populations.
Survival analysis for respiratory failure in patients with food-borne botulism.
Witoonpanich, Rawiphan; Vichayanrat, Ekawat; Tantisiriwit, Kanit; Wongtanate, Manas; Sucharitchan, Niwatchai; Oranrigsupak, Petchdee; Chuesuwan, Aphinya; Nakarawat, Weeraworn; Tima, Ariya; Suwatcharangkoon, Sureerat; Ingsathit, Atiporn; Rattanasiri, Sasivimol; Wananukul, Winai
2010-03-01
Botulism is a rare presynaptic neuromuscular junction disorder caused by potent toxins produced by the anaerobic, spore-forming, Gram-positive bacterium Clostridium botulinum. Food-borne botulism is caused by the ingestion of foods contaminated with botulinum toxin. In March 2006, there was a large outbreak of food-borne botulism associated with the ingestion of home-canned bamboo shoots in Thailand. The survival analyses for respiratory failure in these patients were studied and are reported here. A prospective observational cohort study was conducted on this outbreak. The primary outcome of interest was the time to respiratory failure. The secondary outcome was the time to weaning off ventilator. The prognostic factors associated with respiratory failure and weaning off ventilator are presented. A total of 91 in-patients with baseline clinical characteristics were included. Most cases first presented with gastrointestinal symptoms followed by neurological symptoms, the most striking of which being difficulty in swallowing. Common clinical features included ptosis, ophthalmoplegia, proximal muscle weakness, pupillary abnormality, and respiratory failure. Forty-two patients developed respiratory failure requiring mechanical ventilation and the median duration on ventilator was 14 days. The median length of hospital stay for all patients was 13.5 days. Difficulty in breathing, moderate to severe ptosis, and dilated and fixed pupils were associated with respiratory failure. Among patients who were on ventilators, a short incubation period and pupillary abnormality were associated with a longer period of mechanical ventilation. All patients had antitoxin injection and there was no mortality in this outbreak. The history of difficult breathing and the findings of moderate to severe ptosis and pupillary abnormality were associated with severe illness and respiratory failure. A long incubation time was associated with a better prognosis. Although botulism is a potentially fatal disease, there was no mortality in this outbreak. All patients had antitoxin injection and good intensive care that resulted in good clinical outcomes.
Medical Countermeasure Models. Volume 8. Botulinum Neurotoxin
2013-04-12
Neurologists and the threat of bioterrorism.” Journal of the Neurological Sciences. 249(1). 2006. 9 Smith LA. “Botulism and vaccines for its prevention...toxin as a biological weapon.” Journal of the American Medical Association. 285(1059). 2001. 24 Tacket CO et al. “ Equine Antitoxin Use and Other...antitoxin available for non-infant cases of botulism in the United States.69,70 HBAT, an equine antitoxin, targets BoNT serotypes A, B, C, D, E, F and G
A cluster of three cases of botulism due to Clostridium baratii type F, France, August 2015.
Tréhard, Hélène; Poujol, Isabelle; Mazuet, Christelle; Blanc, Quentin; Gillet, Yves; Rossignol, Frédérique; Popoff, Michel-Robert; Jourdan Da Silva, Nathalie
2016-01-01
A cluster of three cases of food-borne botulism due to Clostridium baratii type F occurred in France in August 2015. All cases required respiratory assistance. Consumption of a Bolognese sauce at the same restaurant was the likely source of contamination. Clostridium baratii was isolated both from stool specimens from the three patients and ground meat used to prepare the sauce. This is the second episode reported in France caused by this rare pathogen.
Acute neuromuscular weakness in a boy with a facial abscess contaminated with Clostridium botulinum.
Olson, Scott C; Bergen, Carly M; Andre-von Arnim, Amelie Saint; D'Angeli, Marisa A; Goldoft, Marcia J; Russell, Denny; Atkins, Robert C
2012-12-01
Wound botulism arising from skin and soft tissue infection is rare in children, most cases being reported in adult intravenous drug users. Cranial nerve palsies are the primary presenting sign, followed by descending neuromuscular weakness. Diagnosis relies on isolation of either toxigenic Clostridium botulinum species or toxin from wound or blood samples. We present an unusual case of wound botulism in a pediatric patient with the intent to inform the reader and improve the time to diagnosis in such cases.
Structure-based drug discovery for botulinum neurotoxins.
Swaminathan, Subramanyam
2013-01-01
Clostridium botulinum neurotoxin is the most poisonous substance known to humans. It is a potential biowarfare threat and a public health hazard. The only therapeutics available is antibody treatment which will not be effective for post-exposure therapy. There are no drugs available for post-intoxication treatment. Accordingly, it is imperative to develop effective drugs to counter botulism. Available structural information on botulinum neurotoxins both alone and in complex with their substrates offers an efficient method for designing structure-based drugs to treat botulism.
Sandler, Renee J.; Rocke, T.E.; Samuel, M.D.; Yuill, Thomas M.
1993-01-01
The prevalence of Clostridium botulinum type C (% of positive sediment samples) was determined in 10 marshes at Sacramento National Wildlife Refuge (SNWR), located in the Central Valley of California (USA), where avian botulism epizootics occur regularly. Fifty-two percent of 2,200 sediment samples collected over an 18-mo period contained C. botulinum type C (both neurotoxic and aneurotoxic) which was present throughout the year in all 10 marshes. The prevalence of C. botulinum type C was similar in marshes with either high or low botulism losses in the previous 5 yr. Marshes with avian botulism mortality during the study had similar prevalences as marshes with no mortality. However, the prevalence of C. botulinum type C was higher in marshes that remained flooded all year (permanent) compared with marshes that were drained in the spring and reflooded in the fall (seasonal). The prevalence of C. botulinum type C declined in seasonal marshes during the dry period. Similar declines did not occur in the permanently flooded marshes.
A brief history of botulism in South Africa.
Cameron, C M
2009-03-01
When looking back into the history of botulism and contemplating the final understanding of the syndrome and the ultimate solutions, there are four facets that stand out clearly. The first is that much of the solution was guided by astute observations, curious travellers, committed veterinarians and particularly farmers themselves who were able to relate the occurrence of the condition to climatic and grazing conditions. Secondly, there was the identification of the osteophagia and pica syndrome which led to the feeding of bone-meal as a successful mitigating measure as well as the establishment that botulism was not due to a plant poisoning. Thirdly, the solution of the problem depended on the integration of experience and knowledge from diverse disciplines such as soil science, animal behaviour and husbandry, nutrition, botany and ultimately advanced bacteriology and the science of immunology. Finally it required the technical advancement to produce toxoids in large quantities and formulate effective aluminium hydroxide precipitated and oil emulsion vaccines.
Oral vaccination with an adenovirus-vectored vaccine protects against botulism
Chen, Shan; Xu, Qingfu; Zeng, Mingtao
2013-01-01
We have previously shown that an adenovirus vectored vaccine delivered intramuscularly or intranasally was effective in protection against botulism in a mouse model. The adenoviral vector encodes a human codon-optimized heavy chain C-fragment (HC50) of botulinum neurotoxin type C (BoNT/C). Here, we evaluate the same vaccine candidate as an oral vaccine against BoNT/C in a mouse model. To elicit protective immunity, the mice were orally vaccinated with a single dose of 1×104 to 1×107 plaque forming units (pfu) of the adenoviral vector. The immune sera, collected six weeks after oral vaccination with 2×107 pfu adenovirus, has shown an ability to neutralize the biological activity of BoNT/C in vitro. Additionally, animals receiving a single dose of 2×106 pfu adenovirus or greater were completely protected against challenge with 100×MLD50 of BoNT/C. The data demonstrated the feasibility to develop an adenovirus-based oral vaccine against botulism. PMID:23295065
Evaluation of synaptophysin as an immunohistochemical marker for equine grass sickness.
Waggett, B E; McGorum, B C; Shaw, D J; Pirie, R S; MacIntyre, N; Wernery, U; Milne, E M
2010-05-01
It has been proposed that synaptophysin, an abundant integral membrane protein of synaptic vesicles, is an immunohistochemical marker for degenerating neurons in equine grass sickness (GS). In the present study, a statistically generated decision tree based on assessment of synaptophysin-immunolabelled ileal sections facilitated correct differentiation of all 20 cases of GS and 24 cases of non-GS disease (comprising eight horses with colic, six with neuroparalytic botulism and 10 controls). This technique also facilitated correct diagnosis of GS in all three cases that had been erroneously classified as having non-GS disease based on conventional interpretation of haematoxylin and eosin-stained cryostat sections of ileal surgical biopsies. Further prospective studies involving larger numbers of horses are required to fully validate this decision tree. In contrast to GS, botulism did not alter ileal neuron density or synaptophysin labelling, indicating that different mechanisms cause neuronal damage and/or dysfunction in GS and botulism. Copyright 2009 Elsevier Ltd. All rights reserved.
Toxicoinfectious botulism in foals and adult horses.
Swerczek, T W
1980-02-01
Toxicoinfectious botulism was proved to be the cause of a neuromuscular paralytic syndrome in foals and adult horses. In eight successive cases, Clostridium botulinum type B was isolated at necropsy. Foals were either found dead without premonitory signs of illness or, most often, they had signs of progressive and symmetric motor paralysis. Stilted gait, muscular tremors, and the inability to stand longer than 4 to 5 minutes were the salient clinical signs. Other clinical manifestations included dysphagia, constipation, mydriasis, and frequent urination. As the disease progressed, dyspnea with extension of the head and neck, tachycardia, and respiratory arrest occurred. Death occurred most often 24 to 72 hours after the onset of clinical signs. The most consistent postmortem findings were congestion and edema of the lungs and excessive pericardial fluid, which contained free-floating strands of fibrin. Gastric ulcers, foci of necrosis in the liver, abscesses in the navel and lungs, and wounds of the skin and muscle were predisposing sites for development of toxicoinfectious botulism.
Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vieni, Casey; McGillick, Brian; Kumaran, Desigan
Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less
Goldberg, Diana R.; Samuel, M.D.; Rocke, T.E.; Johnson, K.M.; Linz, G.
2004-01-01
Blackbird (family lcteridae) depredation on sunflower (Helianthus annuus) crops in the prairie states of the United States has motivated the proposed use of an avicide, DRC-1339 (3-chloro-4-methylaniline), to decrease their numbers. The resulting mortality of blackbirds at wetland roosts could increase the potential of avian botulism occurring in affected marshes. To assess this possibility, we seeded (artificially placed) blackbird carcasses in selected wetlands in Stutsman County, North Dakota, during August-September 2000 and July-September 2001 to evaluate their rate of decomposition and role in initiating avian botulism outbreaks. We monitored carcasses to determine their persistence, the frequency and amount of maggots produced, and the presence of type C botulinum toxin. In 10 of our 12 study wetlands, blackbird carcasses were not rapidly removed by scavengers, thus providing substrate for maggot growth and potential production of Clostridium botulinum toxin. Decomposition of carcasses occurred rapidly, and maggot production averaged 4a??5 g per carcass within 9 days. We were unable to detect C. botulinum type C toxin in any of the 377 blackbird carcasses or the 112 samples of maggots we collected in 2000 or 2001. None of the 25 blackbird carcasses we tested contained botulinum spores, the most probable explanation for the absence of botulinum toxin production. Our results indicate that the likelihood of DRC-1339-poisoned blackbirds causing botulism outbreaks would be minimal in North Dakota wetlands during late summer and early autumn.
Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors
Vieni, Casey; McGillick, Brian; Kumaran, Desigan; ...
2018-02-14
Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less
Hannett, George E.; Stone, Ward B.; Davis, Stephen W.; Wroblewski, Danielle
2011-01-01
The genetic relatedness of Clostridium botulinum type E isolates associated with an outbreak of wildlife botulism was studied using random amplification of polymorphic DNA (RAPD). Specimens were collected from November 2000 to December 2008 during a large outbreak of botulism affecting birds and fish living in and around Lake Erie and Lake Ontario. In our present study, a total of 355 wildlife samples were tested for the presence of botulinum toxin and/or organisms. Type E botulinum toxin was detected in 110 samples from birds, 12 samples from fish, and 2 samples from mammals. Sediment samples from Lake Erie were also examined for the presence of C. botulinum. Fifteen of 17 sediment samples were positive for the presence of C. botulinum type E. Eighty-one C. botulinum isolates were obtained from plants, animals, and sediments; of these isolates, 44 C. botulinum isolates produced type E toxin, as determined by mouse bioassay, while the remaining 37 isolates were not toxic for mice. All toxin-producing isolates were typed by RAPD; that analysis showed 12 different RAPD types and multiple subtypes. Our study thus demonstrates that multiple genetically distinct strains of C. botulinum were involved in the present outbreak of wildlife botulism. We found that C. botulinum type E is present in the sediments of Lake Erie and that a large range of bird and fish species is affected. PMID:21115703
A case of type F botulism in southern California.
Richardson, William H; Frei, Shermane S; Williams, Saralyn R
2004-01-01
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. 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. 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.
[Food-borne botulism: review of five cases].
Cardoso, Teresa; Costa, Manuela; Almeida, H Cristina; Guimarães, Mário
2004-01-01
Food-borne botulism is a disease caused by the ingestion of food contaminated with botulinum toxin, often present in smoked meat, canned food and preserved food; it can occur as sporadic case or as an outbreak. In the last decades there has been an increasing incidence of food-borne botulism in Portugal. The authors do a review of five cases of food-borne botulism, three isolated cases and 2 familiar. Four were associated with the ingestion of smoked ham and one of canned tunafish. The incubation period was 48 hours in one patient and 4 days in another, in the remaining patients it was not possible to determine this period. The clinical picture was dominated in all patients by diplopy, dysphagia, dizziness, blurred vision, dry mouth and constipation, and in two patients there were gastrointestinal complains. In one patient the electromyography findings were compatible with pre-synaptic neuromuscular blockage. A toxin type B was found in the serum of one patient and in the food involved in the two familiar cases. All patients experienced complete recovery with only symptomatic treatment. With this article the authors intend to call attention to this diagnosis, which is not rare, but difficult for someone not familiar with its presentation, being of notice that the diagnosis is essentially clinic with a strong epidemiological history, confirmed by typical electromyography findings and by the identification of the toxin involved. In Portugal there is only descriptions of clinical cases associated with the type B and the type E toxins, not being necessary the resource to the antitoxin therapy.
Acute paralysis following "a bad potato": a case of botulism.
Bhutani, Mohit; Ralph, Edward; Sharpe, Michael D
2005-04-01
Intensivists often encounter patients with respiratory failure as a result of neuromuscular disease, however, acute neuro-muscular syndromes are less common. We present a case of food borne Clostridium botulism and discuss the diagnostic and therapeutic considerations. A 35-yr-old healthy male presented with abdominal pain and blurred vision 12 hr after ingesting a "bad" potato. During the next 17 hr, the patient demonstrated a gradual descending paralysis which ultimately resulted in no cranial nerve function and 0/5 strength in all extremities. Sensation was intact. The patient required intubation and mechanical ventilation. His blood count, biochemical profile, computerized tomography and magnetic resonance imaging of the head were normal. A lumbar puncture revealed no abnormalities. Due to the rapid deterioration and presentation of 'descending' paralysis, botulism was suspected. The patient was treated empirically with botulinum anti-toxin. Samples of blood, stool and gastric contents were cultured for the presence of Clostridium botulinum and its toxin and these tests were positive for botulinum toxin A 12 days later. The patient's neuromuscular function gradually improved over a prolonged period of time. Six and one-half months after his initial presentation, the patient was discharged home after completing an aggressive rehabilitation program. Botulism is a rare syndrome and presents as an acute, afebrile, descending paralysis beginning with the cranial nerves. If suspected, botulinum anti-toxin should be considered, particularly within the first 24 hr of onset of symptoms. Confirmation of the presence of botulinum requires days therefore the diagnosis and management rely on history and physical examination.
Reoccurrence of botulinum neurotoxin subtype A3 inducing food-borne botulism, Slovakia, 2015.
Mad'arová, Lucia; Dorner, Brigitte G; Schaade, Lars; Donáth, Vladimír; Avdičová, Mária; Fatkulinová, Milota; Strhársky, Jozef; Sedliačiková, Ivana; Klement, Cyril; Dorner, Martin B
2017-08-10
A case of food-borne botulism occurred in Slovakia in 2015. Clostridium botulinum type A was isolated from three nearly empty commercial hummus tubes. The product, which was sold in Slovakia and the Czech Republic, was withdrawn from the market and a warning was issued immediately through the European Commission's Rapid Alert System for Food and Feed (RASFF). Further investigation revealed the presence of botulinum neurotoxin (BoNT) subtype BoNT/A3, a very rare subtype implicated in only one previous outbreak (Loch Maree in Scotland, 1922). It is the most divergent subtype of BoNT/A with 15.4% difference at the amino acid level compared with the prototype BoNT/A1. This makes it more prone to evading immunological and PCR-based detection. It is recommended that testing laboratories are advised that this subtype has been associated with food-borne botulism for the second time since the first outbreak almost 100 years ago, and to validate their immunological or PCR-based methods against this divergent subtype. This article is copyright of The Authors, 2017.
Presynaptic Disorders: Lambert-Eaton Myasthenic Syndrome and Botulism.
Gable, Karissa L; Massey, Janice M
2015-08-01
Lambert-Eaton myasthenic syndrome (LEMS) and botulism are acquired presynaptic nerve terminal disorders of the neuromuscular junction. Lambert-Eaton myasthenic syndrome is an idiopathic or paraneoplastic autoimmune syndrome in which autoantibodies of the P/Q-type voltage-gated calcium channel play a role in decreasing the release of acetylcholine, resulting in clinical symptoms of skeletal muscle weakness, diminished reflexes, and autonomic symptoms. Paraneoplastic LEMS is most often associated with small cell lung cancer. Diagnosis is confirmed by positive serologic testing and electrophysiological studies, which display characteristic features of low compound muscle action potentials, a decrement at 3Hz repetitive nerve stimulation, and facilitation with exercise or high-frequency repetitive stimulation. Treatment involves cancer monitoring and treatment, 3,4-diaminopyridine, immunosuppressive medications, and acetylcholinesterase inhibitors. Botulism is another presynaptic disorder of neuromuscular transmission. Clinical features classically involve cranial and bulbar palsies followed by descending weakness of the limbs, respiratory failure, and autonomic dysfunction. Electrodiagnostic testing is important in the evaluation and diagnosis. Treatment is supportive, and administration of antitoxin is beneficial in selected cases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
[Botulism. Summary based on six cases].
Adorján, T; Farkas, M; Boros, L; Czeglédi, Z
1998-10-18
Botulism is a rare neuroparalytic disease caused by neurotoxins of Clostridium species. In Hungary it most commonly occurs as a foodborne illness with ocular and bulbar paralysis, muscle weakness and gastrointestinal symptoms. Six cases of botulism were observed by the authors, first in 1993 five members of a family, then in 1997 a patient with sporadic illness. The diagnosis was confirmed by toxin tests in addition to the symptoms and food history. Recognition of the epidemiologic associations proved very useful in the confirmation of outbreak-related cases. The illness was moderately serious at three patients and mild at two patients. One of the patients had a cirrhosis of the liver, and her status became critical because of the repeated bleeding from oesophagus varicose vein. The patient with sporadic illness had a serious gastric dilatation and palsy of bowels causing paralytic ileus at the start of the illness. The symptoms regressed slowly, roughly in three weeks, at all patients. Death did not happened. After the case reports the authors review the disease-microorganism, toxin, clinical entities, incidence, symptoms, diagnosis, differential-diagnosis, and finally the treatment.
Immunization of ducks for type C botulism.
Martinez, R; Wobeser, G
1999-10-01
A single subcutaneous immunization with a vaccine used for protecting ranch mink (Mustela vison) against type C botulism reduced morbidity and mortality in mallard (Anas platyrhynchos) and northern pintail (Anas acuta) ducks challenged with approximately 4.5 x 10(4) and 2.25 x 10(4) mouse lethal doses (MLD50), respectively, of botulinum toxin at 10 and 15 days post-immunization (pi). There was no significant protection at 5 days pi. Protection persisted in mallards for 90 days pi. To simulate use of vaccine as a part of treatment of sick birds in the field, mallards were exposed to toxin and, when clinical signs were evident, each bird was treated by intraperitoneal injection of type C botulinum antitoxin and one-half of the birds were immunized. Immunization had no significant effect on recovery from intoxication. At 10 days posttreatment, all birds were challenged with toxin. Clinical signs and mortality were significantly less frequent among immunized birds than among non-immunized birds after the second exposure. Immunization might be useful as part of the treatment regimen in botulism outbreaks.
... western equine encephalitis Botulism Brucellosis Chancroid Chickenpox Chlamydia Cholera Coccidioidomycosis Cryptosporidiosis Cyclosporiasis Diphtheria Giardiasis Gonorrhea Haemophilus influenza, ...
THE INFLUENCE OF CALCIUM CHLORIDE UPON EXPERIMENTAL BOTULISM
Hall, Ivan C.; Davis, Nelson C.
1923-01-01
1. Calcium chloride given subcutaneously, intraperitoneally, or intravenously has been found to have no effect upon the production of botulism following the injection of Bacillus botulinus (Strain 80B) into the peritoneal cavity of guinea pigs. 2. Treatment of Bacillus botulinus with alcohol has been found markedly to decrease its toxicity for guinea pigs. This is in conformity with the work of Bronfenbrenner and Schlesinger. 3. Toxin-free spores of Bacillus botulinus have been found pathogenic for guinea pigs. 4. No prejudice as to possible results in rabbits should be based upon the above conclusions. PMID:19868746
Ineffectiveness of 3,4-diaminopyridine as a therapy for type C botulism.
Siegel, L.S.; Price, J.I.
1987-01-01
Clostridium botulinum neurotoxins inhibit acetylcholine release at neuromuscular junctions. Agents stimulating neurotransmitter efflux, such as 3,4-diaminopyridine (3,4-DAP), could be useful for botulism therapy. Treatment with 3,4-DAP (8 mg/kg hourly, beginning 3 hr after toxin injection) failed to increase the survival times of mice receiving 10, 20 or 40 LD50 type C, but did prolong the survival of those receiving 20 LD50 type A. This difference in 3,4-DAP efficacy may reflect variations in the molecular mechanism of action of types A and C botulinum neurotoxins.
Avian disease at the Salton Sea
Friend, M.
2002-01-01
A review of existing records and the scientific literature was conducted for occurrences of avian diseases affecting free-ranging avifauna within the Salton Sea ecosystem. The period for evaluation was 1907 through 1999. Records of the U.S. Department of Agriculture, Bureau of Biological Survey and the scientific literature were the data sources for the period of 1907a??1939. The narrative reports of the U.S. Fish and Wildlife Service's Sonny Bono National Wildlife Refuge Complex and the epizootic database of the U.S. Geological Survey's National Wildlife Health Center were the primary data sources for the remainder of the evaluation. The pattern of avian disease at the Salton Sea has changed greatly over time. Relative to past decades, there was a greater frequency of major outbreaks of avian disease at the Salton Sea during the 1990s than in previous decades, a greater variety of disease agents causing epizootics, and apparent chronic increases in the attrition of birds from disease. Avian mortality was high for about a decade beginning during the mid-1920s, diminished substantially by the 1940s and was at low to moderate levels until the 1990s when it reached the highest levels reported. Avian botulism (Clostridium botulinum type C) was the only major cause of avian disease until 1979 when the first major epizootic of avian cholera (Pasteurella multocidia) was documented. Waterfowl and shorebirds were the primary species affected by avian botulism. A broader spectrum of species have been killed by avian cholera but waterfowl have suffered the greatest losses. Avian cholera reappeared in 1983 and has joined avian botulism as a recurring cause of avian mortality. In 1989, avian salmonellosis (Salmonella typhimurium) was first diagnosed as a major cause of avian disease within the Salton Sea ecosystem and has since reappeared several times, primarily among cattle egrets (Bubulcus ibis). The largest loss from a single epizootic occurred in 1992, when an estimated 155thinsp000 birds, primarily eared grebes (Podiceps nigricollis), died from an undiagnosed cause. Reoccurrences of that unknown malady have continued to kill substantial numbers of eared grebes throughout the 1990s. The first major epizootic of type C avian botulism in fish-eating birds occurred in 1996 and killed large numbers of pelicans (Pelecanus occidentalis & P. erythrorhynchos). Avian botulism has remained as a major annual cause of disease in pelicans. In contrast, the chronic on-Sea occurrence of avian botulism in waterfowl and shorebirds of previous decades was seldom seen during the 1990s. Newcastle disease became the first viral disease to cause major bird losses at the Salton Sea when it appeared in the Mullet Island cormorant (Phalacrocorax auritus) breeding colony during 1997 and again during 1998.
Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum
Carter, Andrew T; Paul, Catherine J; Mason, David R; Twine, Susan M; Alston, Mark J; Logan, Susan M; Austin, John W; Peck, Michael W
2009-01-01
Background Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Results Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic C. botulinum and the closely related C. sporogenes tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to C. sporogenes), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI. Conclusion Proteolytic C. botulinum has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic C. botulinum, and is suitable for clinical and forensic investigations of botulism outbreaks. PMID:19298644
Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum.
Carter, Andrew T; Paul, Catherine J; Mason, David R; Twine, Susan M; Alston, Mark J; Logan, Susan M; Austin, John W; Peck, Michael W
2009-03-19
Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic C. botulinum and the closely related C. sporogenes tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to C. sporogenes), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI. Proteolytic C. botulinum has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic C. botulinum, and is suitable for clinical and forensic investigations of botulism outbreaks.
Payne, J H; Hogg, R A; Otter, A; Roest, H I J; Livesey, C T
2011-06-18
Scanning surveillance by the Veterinary Laboratories Agency revealed the emergence of suspected botulism in ruminants in 2003, presented as flaccid paralysis. From 2003 to 2009, 168 cattle and 19 sheep incidents were recorded, with mortality between 5 and 80 per cent. All sheep incidents and 95 per cent of cattle incidents had proximity to broiler litter. From July 2006, the gut contents collected from 74 affected cattle and 10 affected sheep were tested for Clostridium botulinum toxins using mice bioassays and for organisms by culture. Type D toxin was identified in 32 per cent of cattle and 18 per cent of sheep samples. C botulinum type D organisms were identified in 40 per cent of cattle and 30 per cent of sheep samples, but broth from one sample reacted with C and D antisera. Type C botulism has previously been reported more commonly than type D in the UK and has been associated with the use of poultry litter as fertiliser, bedding or feed. The almost exclusive association with C botulinum type D toxins or organisms in the gut contents in this survey suggests a change in the source or epidemiology of botulism in the UK. The source of C botulinum type D was uncertain. Broilers may carry C botulinum type D in their gut flora subclinically. The emergence of a new type D strain, or changes in broiler husbandry and nutrition, medication and other enteric infections may have affected colonisation with C botulinum. Further investigation of poultry and farm environments for sources of type D awaits the development of tests for C botulinum toxins that do not require the use of mice.
Waterbird mortality from botulism type E in Lake Michigan: An update
Brand, Christopher J.; Duncan, Ruth M.; Garrow, Scott P.; Olson, Dan; Schumann, Leonard E.
1983-01-01
Three outbreaks of botulism type E occurring in waterbirds on Lake Michigan since autumn 1976 are discussed. Natural ingestion of food containing type E toxin by Ring-billed Gulls (Larus delawarensis) and the presence of type E toxin in blood from moribund gulls were demonstrated. Concurrent presence of type C and type E botulinal toxins was found in a die-off of Common Loons (Gavia immer). In combination with previous reported outbreaks, these incidents suggest that this disease is geographically widespread in Lake Michigan, and that environmental conditions conducive to type E botulinal toxin production and consumption occur in both summer and autumn.
Determination of the median toxic dose of type C botulism in lactating dairy cows
Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, Tonie E.; Galey, F.D.; Cullor, J.S.; Ardans, A.A.
2003-01-01
Because of the difficulty in identifying botulinum toxin in cattle, it is hypothesized that cattle are sensitive to levels of toxin below the detection limits of current diagnostic techniques (the mouse protection bioassay and the immunostick enzyme-linked immunosorbent assay [ELISA] for type C botulinum toxin). Using an up-down method for toxicologic testing, the median toxic dose (MTD50) for cattle was determined. Four lactating Holstein cows were dosed at 0.125 or 0.25 ng/kg with Clostridium botulinum type C toxin and failed to develop clinical signs of botulism during the 7-day observation period. Three cows given 0.50 ng/kg of toxin developed clinical signs of botulism. From these results, the MTD50 was calculated at 0.388 ng/kg (3.88 mouse lethal doses/kg) using the trim-logit method. These results suggest that cattle are 12.88 times more sensitive to type C botulinum toxin than a mouse on a per kilogram weight basis. The mouse protection bioassay and the immunostick ELISA for type C botulinum toxin failed to identify the presence of the toxin in the serum, blood, and milk samples taken from all 7 animals.
Feng, Ling; Chen, Xueping; Liu, Shujie; Zhou, Zengrong; Yang, Rong
2015-01-01
On September 22, 2013, two patients from Sichuan Province, China presented with symptoms of food-borne botulism, a rare but fatal illness caused by the consumption of foods containing Clostridium botulinum neurotoxins. Investigators reviewed the medical charts and food consumption histories, and interviewed patients and family members. Food samples and clinical specimens were tested for botulinum toxin and neurotoxin-producing Clostridium species by standard methods. The first two index cases presented with cranial neuropathies and flaccid paralysis, and required mechanical ventilation. There were 12 confirmed outbreak-associated cases. Botulinum toxin type A was identified in the smoked ribs, and all of the patients had consumed the smoked ribs from the same local restaurant. The smoked ribs contained no added salt, sugar, or preservative. Botulinum toxin production likely resulted from the cold-smoking preparation method and inappropriate refrigeration. Smoked ribs produced by a local restaurant, contaminated with type A botulism, was the contributor to this outbreak. The supervision of food safety should be strengthened to prevent future outbreaks in China. Copyright © 2014 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Outbreak of Type C Botulism in Commercial Layer Chickens.
Sato, Yuko; Wigle, William L; Gallagher, Susan; Johnson, Amy L; Sweeney, Raymond W; Wakenell, Patricia S
2016-03-01
This report describes an outbreak of type C botulism in two organic, free-range commercial layer farms in the Midwest. Hens affected were 64-wk-old Hy-Line brown hens and 34-wk-old Hy-Line brown hens owned by the same company, but housed on different premises, with approximately 20,000 birds per house. Mortality over the 2 wk of investigation was estimated to be up to 8% and 2.8%, respectively, with birds acting listless, lethargic, and depressed. Clinical signs consisted of progressive paralysis, and severely affected birds were moribund and laterally recumbent. Hens had ruffled feathers that easily epilated, with loss of muscular tone in the neck, tail, and wings. Hens had closed eyes and were reluctant to move. There were no significant gross or histopathologic lesions. Intestinal samples were submitted to the University of Pennsylvania Botulism Diagnostic Laboratory for real-time PCR and were positive for Clostridium botulinum organisms containing the Type C neurotoxin gene. Speculations on the source of the botulinum toxins include poor mortality removal leading to cannibalism of decomposing carcasses, as well as birds on the farm having access to putrid carcasses in the compost pile from a hole in their outdoor access fence.
Work, Thierry M.; Klavitter, John L.; Reynolds, Michelle H.; Blehert, David S.
2010-01-01
Laysan Ducks are endemic to the Hawaiian archipelago and are one of the world’s most endangered waterfowl. For 150 yr, Laysan Ducks were restricted to an estimated 4 km2 of land on Laysan Island in the northwestern Hawaiian Islands. In 2004 and 2005, 42 Laysan Ducks were translocated to Midway Atoll, and the population increased to approximately 200 by 2007. In August 2008, mortality due to botulism type C was identified, and 181 adult, fledgling, and duckling carcasses were collected from August to October. Diseased birds were found on two islands within Midway Atoll at multiple wetlands; however, one wetland contributed most carcasses. The epidemic was discovered approximately 14–21 days after the mortality started and lasted for 50 additional days. The details of this epidemic highlight the disease risk to birds restricted to small island populations and the challenges associated with managing newly translocated endangered species. Frequent population monitoring for early disease detection and comprehensive wetland monitoring and management will be needed to manage avian botulism in endangered Laysan Ducks. Vaccination may also be beneficial to reduce mortality in this small, geographically closed population.
[Botulinum toxin: from drug to poison].
Dressler, D; Saberi, F A
2009-08-01
For most of its time, the history of botulinum toxin (BT) has been the history of botulism, i. e. of an intoxication with BT. By the end of the 1960's a paradigm shift took place which in this radicalness had never occurred before in the history of mankind. At that time BT was first used therapeutically to treat strabismus. From ophthalmology BT rapidly spread into numerous medical specialties. For most of its indications BT is the therapy of choice, for some it has revolutionized their treatment altogether. The widespread therapeutic use of BT allowed detailed clinical and technical investigations of BT's action upon the human body. Applying this knowledge we diagnosed for the first time chronic botulism in adults living on a farm with chronic bovine botulism. This constitutes another radical paradigm shift. The history of BT is the history of a dual paradigm shift each time induced by a complete reversal of the viewing perspective. Knowledge gain can be a linear process. It can, however, also be a circular one. Changes of the viewing perspective are crucial. Changing the viewing perspective may facilitate knowledge gain. This might be used to develop an instrument to facilitate knowledge gain. (c) Georg Thieme Verlag KG Stuttgart-New York.
Auricchio, Bruna; Woudstra, Cédric; Fach, Patrick; Fiore, Alfonsina; Skarin, Hanna; Bano, Luca; Segerman, Bo; Knutsson, Rickard; De Medici, Dario
2013-01-01
Botulism is a neuroparalytic disease that can occur in all warm-blooded animals, birds, and fishes. The disease in animals is mainly caused by toxins produced by Clostridium botulinum strains belonging to group III, although outbreaks due to toxins produced by group I and II organisms have been recognized. Group III strains are capable of producing botulinum toxins of type C, D, and C/D and D/C mosaic variants. Definitive diagnosis of animal botulism is made by combining clinical findings with laboratory investigations. Detection of toxins in clinical specimens and feed is the gold standard for laboratory diagnosis. Since toxins may be degraded by organisms contained in the gastrointestinal tract or may be present at levels below the detection limit, the recovery of C. botulinum from sick animal specimens is consistent for laboratory confirmation. In this article we report the development and in-house validation of a new multiplex real-time PCR for detecting and typing the neurotoxin genes found in C. botulinum group III organisms. Validation procedures have been carried out according to ISO 16140, using strains and samples recovered from cases of animal botulism in Italy and France. PMID:23971808
Bianco, M I; Lúquez, C; De Jong, L I T; Fernández, R A
2009-01-01
Infant botulism is an intestinal toxemia caused principally by Clostridium botulinum. Since the infection occurs in the intestinal tract, numerous food products have been investigated for the presence of C. botulinum and its neurotoxins. In many countries, people use linden flower (Tilia spp) tea as a household remedy and give it to infants as a sedative. Therefore, to help provide a clear picture of this disease transmission, we investigated the presence of botulinum spores in linden flowers. In this study, we analyzed 100 samples of unwrapped linden flowers and 100 samples of linden flowers in tea bags to determine the prevalence and spore-load of C. botulinum. Results were analyzed by the Fisher test. We detected a prevalence of 3% of botulinum spores in the unwrapped linden flowers analyzed and a spore load of 30 spores per 100 grams. None of the industrialized linden flowers analyzed were contaminated with botulinum spores. C. botulinum type A was identified in two samples and type B in one sample. Linden flowers must be considered a potential vehicle of C. botulinum, and the ingestion of linden flower tea can represent a risk factor for infant botulism.
Duncan, Ruth M.; Jensen, Wayne I.
1976-01-01
A survey of the sources of Clostridium botulinum type C toxin possibly utilized as food by aquatic birds in an epizootic area of avian botulism in northern Utah showed that living aquatic and terrestrial invertebrates normally found in close association with dead, decomposing birds commonly carried the toxin. Of 461 samples associated with 21 species of avian carcasses, 198 were toxin-positive. Invertebrate species not normally scavengers of vertebrate tissues were less commonly and less highly toxic, particularly when captured 30 cm or more from a carcass; six of 237 samples of such aquatic invertebrates contained low-level toxin. Of the species tested, blow fly larvae (Calliphoridae) were the most consistently and highly toxic, although others, particularly adult and larval stages of several species of beetles (Coleoptera), contained toxin at levels probably significant in the epizootiology of the disease. An estimated 0.05 to 0.25 g of the most toxic fly larvae or 15 g of the most toxic beetles tested carried a mediam lethal dose for an adult mallard duck. Examination of stomach contents of aquatic birds dead of botulism showed that some had consumed invertebrates.
Evaluation of Potential Risk of Botulism from Seafood Cocktails
Lerke, Peter
1973-01-01
Clostridium botulinum E could not be detected in 35 samples of commercial seafood cocktails, ranging in pH from 4.10 to 4.85. At 30 C, toxinogenesis in homogenates acidified with a citric-acetic acid mixture was prevented at pH 4.86 or lower for crabmeat and at 5.03 or lower for shrimp. Measurements of the rate of acid penetration into the centers of large pieces of flesh indicated that the already small risk of botulism from seafood cocktails could be completely eliminated by using a cocktail sauce at a maximum pH of 3.70 and by cooling the final product to at least 10 C for 24 h. PMID:4577180
Personne, M
2000-03-22
The last camp of the three members of the 1897 Swedish Andrée balloon expedition to the North Pole was found in Svalbard in 1930. The human remains and the paraphernalia of the expedition including diaries were brought to Sweden and are presently housed in a museum. The cause of the deaths has never been determined, but several hypotheses have been put forward over the years. Trichinosis, scurvy, and poisoning by carbon-monoxide, vitamin-A or lead are some of them. In this article it is argued that botulism is a plausible explanation which is in better accord with known facts.
Wound botulism presenting as a deep neck space infection.
Gouveia, Christopher; Mookherjee, Somnath; Russell, Matthew S
2012-12-01
Otolaryngologists commonly evaluate patients with findings suspicious for deep space soft tissue infections of the neck. In this case, a woman with a history of injection drug use (IDU) presented with dysphagia, odynophagia, and neck pain. Multiple neck abscesses, too small to drain, were seen on imaging. Despite broad-spectrum intravenous antibiotics, she unexpectedly and rapidly developed respiratory failure requiring intubation. Further work-up diagnosed wound botulism (WB). To our knowledge, this is the first report of WB presenting as a deep neck space infection, and illustrates the importance of considering this deadly diagnosis in patients with IDU history and bulbar symptoms. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Yule, Adam M; Barker, Ian K; Austin, John W; Moccia, Richard D
2006-07-01
Since 1999, large-scale mortalities of fish-eating birds have been observed on the Great Lakes, and more specifically on Lake Erie. Type E botulism has been established as the primary cause of death. The mechanism of type E botulism exposure in fish-eating birds is unclear. Given that these birds are thought to eat live fish exclusively, it seems likely that their prey play a key role in the process, but the role of fish as potential transport vectors of botulinum neurotoxin type E (BoNT/E) to birds has not been adequately investigated. Between June 2003 and April 2004 a methodological model for exposing fish to Clostridium botulinum was developed and used to compare the sensitivity of rainbow trout (Oncorhynchus mykiss), round goby (Neogobius melanostomas), walleye (Stizostedion vitreum), and yellow perch (Perca flavescens) to four doses (0, 800, 1,500, and 4,000 Mouse Lethal Doses) of Clostridium botulinum type E neurotoxin. Each fish species expressed unique changes in both behavior and skin pigmentation prior to death. Yellow perch survived significantly longer (P < 0.05) than the three other species at all toxin treatments. Results of this study suggest that live fish can represent a significant vector for transfer of BoNT/E to birds.
An outbreak of type C botulism in Herring Gulls (Larus argentatus) in Southeastern Sweden
Neimanis, A.; Gavier-Widen, D.; Leighton, F.; Bollinger, T.; Rocke, Tonie E.; Morner, T.
2007-01-01
From 2000 to 2004, over 10,000 seabirds, primarily Herring Gulls (Larus argentatus), died from an undetermined cause in the Blekinge archipelago in southeastern Sweden. In June 2004, 24 affected Herring Gulls were examined clinically, killed humanely, and 23 were examined by necropsy. Seven and 10 unaffected Herring Gulls collected from a local landfill site and from Iceland, respectively, served as controls. All affected birds showed similar neurologic signs, ranging from mild incoordination and weakness to severe flaccid paralysis of legs and wings, but generally were alert and responsive. All affected gulls were in normal nutritional condition, but were dehydrated and had empty stomachs. No gross or microscopic lesions, and no bacterial or viral pathogens were identified. Type C botulinum toxin was detected in the sera of 11 of 16 (69%) affected gulls by mouse inoculation. Type C botulism was the proximate cause of disease in 2004. Sera from 31% of birds tested from outbreaks in 2000 to 2003 also had detectable type C botulinum toxin by mouse inoculation. No large-scale botulism outbreak has been documented previously in this area. The source of toxin, initiating conditions, and thus, the ultimate cause of this outbreak are not known. This epidemic might signal environmental change in the Baltic Sea.
Greenblatt, Daniel; Krupp, Lauren B; Belman, Anita L
2013-01-01
Parainfectious disorders of the nervous system encompass those meningo-encephalo-radiculomyelitic conditions that are temporally associated with a systemic infection, antigenic stimuli, or toxin exposure, in the absence of evidence of direct neuronal infection or invasion of the central nervous system (CNS) or peripheral nervous system (PNS). Pathogenetic mechanisms can be due to immune-mediated processes (such as bystander activation, molecular mimicy) or the inciting insult can be due to toxic factors, as in the case of botulism. A myriad of clinical manifestations can occur including headache, seizures, and mental status changes, ranging from mood and behavioral disturbances to varying levels of alteration in consciousness. Focal neurological deficits can include aphasia, hemiparesis, or paraparesis. The PNS can also be affected leading to cranial nerve involvement, focal or multifocal neuropathies, and dysfunction of the autonomic nervous system. Diagnosis is based not only on the history, examination, laboratory, and neuroimaging data but also on epidemiological factors. The parainfectious disorders covered in this review are cat scratch disease, Lyme borreliosis, legionellosis, brucellosis, botulism, pertussis, and mycoplasma. Each is associated with a distinct organism, has both systemic and neurological manifestations, and has a different epidemiological profile. Copyright © 2013 Elsevier B.V. All rights reserved.
From poison to remedy: the chequered history of botulinum toxin.
Erbguth, F J
2008-01-01
Botulinum toxin poisoning has afflicted mankind through the mists of time. However, the first incident of food-borne botulism was documented as late as the 18th century, when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The district medical officer Justinus Kerner (1786--1862), who was also a well-known German poet, published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822 and attributed the intoxication to a biological poison. Kerner also postulated that the toxin might be used for treatment purposes. In 1895, an outbreak of botulism in the small Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the type-A serotype was used in medicine to correct strabismus. Other preparations of the type-A toxin were developed and manufactured in the United Kingdom, Germany, and China, whereas a therapeutic type-B toxin was prepared in the United States. To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.
An outbreak of type C botulism in herring gulls (Larus argentatus) in southeastern Sweden.
Neimanis, A; Gavier-Widén, D; Leighton, F; Bollinger, T; Rocke, T; Mörner, T
2007-07-01
From 2000 to 2004, over 10,000 seabirds, primarily Herring Gulls (Larus argentatus), died from an undetermined cause in the Blekinge archipelago in southeastern Sweden. In June 2004, 24 affected Herring Gulls were examined clinically, killed humanely, and 23 were examined by necropsy. Seven and 10 unaffected Herring Gulls collected from a local landfill site and from Iceland, respectively, served as controls. All affected birds showed similar neurologic signs, ranging from mild incoordination and weakness to severe flaccid paralysis of legs and wings, but generally were alert and responsive. All affected gulls were in normal nutritional condition, but were dehydrated and had empty stomachs. No gross or microscopic lesions, and no bacterial or viral pathogens were identified. Type C botulinum toxin was detected in the sera of 11 of 16 (69%) affected gulls by mouse inoculation. Type C botulism was the proximate cause of disease in 2004. Sera from 31% of birds tested from outbreaks in 2000 to 2003 also had detectable type C botulinum toxin by mouse inoculation. No large-scale botulism outbreak has been documented previously in this area. The source of toxin, initiating conditions, and thus, the ultimate cause of this outbreak are not known. This epidemic might signal environmental change in the Baltic Sea.
Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J
2013-03-19
Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism outbreaks in birds.
Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Tepp, William H.; Lin, Guangyun; Johnson, Eric A.; Peller, Julie; Sadowsky, Michael J.
2013-01-01
Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15 000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism outbreaks in birds.
New dimensions in diseases affecting waterfowl
Friend, Milton
1975-01-01
We start off with light heart, but as we near the marsh, we stop abruptly in shock and horror. The shoreline, where only last evening we saw thousands of sleek, apparently healthy birds, is now littered with their bodies. Most of them are ducks, but here and there we see a Canada goose, a gull, an avocet, a black-necked stilt, a pelican.....This is the way Jensen and Williams (1964) described an outbreak of avian botulism in a western marsh. It illustrates, more vividly than dry facts and body counts, the impact a disease can have on a population of waterfowl.When we think about waterfowl diseases, we probably think first of botulism and then of lead poisoning, the result of birds swallowing spent lead shot. In fact, these are the only two diseases discussed by Kortright (1942) and Day (1949) in major books on North American waterfowl, attesting to both their importance and our years of experience with them. Botulism was probably an old problem in 1910, but the catastrophic loss that summer of millions of aquatic birds near the Great Salt Lake and in California marked the beginning of real concern about its impact on waterfowl populations (Jensen and Williams, 1964). Concern about lead poisoning of waterfowl began a few years later following the investigations of Wetmore (1919).Today, more than 50 years after these early reports, botulism and lead poisoning are still major disease problems of North American waterfowl, but they are no longer the only ones. After years of study, we have learned much about how these two diseases occur and about their prevention and control. But now there are new pathogens and new toxic compounds that can afflict waterfowl populations. So rather than redescribe the established disease problems of the past and present, I will concentrate on some of these new waterfowl disease problems of the present and future.
A bovine botulism outbreak associated with a suspected cross-contamination from a poultry farm.
Souillard, R; Le Maréchal, C; Ballan, V; Mahé, F; Chemaly, M; Le Bouquin, S
2017-09-01
In October 2014, an outbreak of botulism type D/C occurred on two cattle farms in close proximity. A poultry farm located nearby with no history of botulism had transferred poultry manure to both bovine farms before the beginning of the outbreak. Given this context, epidemiological investigation was conducted to determine if the poultry farm was a reservoir of C. botulinum type D/C and to identify the source of contamination on the cattle farms. Environmental samples were collected at three houses on the poultry farm (boot swabs from the surroundings, swabs from the ventilation system, boot swabs from the poultry litter and darkling beetles samples), and on the two cattle farms (silage samples, boot swabs from the cattle stalls, boot swabs from the cattle pasture and poultry manure samples). These samples were analyzed using real-time PCR after an enrichment step to detect C. botulinum type D/C. On the poultry farm, three boot swabs from the surroundings, two swabs from the ventilation system, one boot swab from the litter and one sample of darkling beetles were detected positive. On one cattle farm, C. botulinum type D/C was identified in a sample of silage made from grass grown on a field on which the poultry manure had previously been stored and in a boot swab from a pasture. On the other cattle farm, C. botulinum type D/C was detected in a sample of poultry manure stored on the cattle farm and in a boot swab from a pasture. This investigation shows that the healthy poultry farm might have been the reservoir of C. botulinum type D/C and that cross-contamination between poultry and cattle likely occurred, resulting in the botulism outbreak on the two cattle farms. Copyright © 2017 Elsevier B.V. All rights reserved.
Descending polyneuropathy in an intravenous drug user.
O'Sullivan, Jean M; McMahon, Geraldine
2005-10-01
A 27-year-old male intravenous drug user presented to the Emergency Department of St James's Hospital with a 1-week history of progressive dysphasia, dysphagia and difficulty 'holding his head up' and 'keeping his eyes open'. He also complained of increasing weakness in his upper limbs, as a result of which he kept dropping things. He was on a methadone program but was using both intravenous heroin and cocaine at the time of presentation. Examination of his motor function revealed generalized hypotonia, hyporeflexia and reduced power in both upper limbs. No sensory loss was observed. Co-ordination was intact. The clinical picture of a proximal symmetrical descending weakness and an absence of sensory loss was suggestive of botulism. Clostridium botulinum is a spore-forming, obligate anaerobe. The three forms of human botulism are food-borne, wound and intestinal. A fourth man-made form is produced from aerosolized botulinum toxin and results in inhalational botulism. A little as 1 g of aerosolized botulinum toxin has the potential to kill 1.5 million people. Toxin is detected in serum or stool specimens in only approximately 46% of clinically diagnosed cases. Treatment involves supportive care and early passive immunization with equine antitoxin. Patients should be regularly assessed for loss of gag and cough reflex, control of oropharyngeal secretions, oxygen saturation, vital capacity and inspiratory force. When respiratory function begins to deteriorate, anticipatory intubation is indicated. Early symptom recognition and early treatment with antitoxin are essential in order to prevent mortality, and to prevent additional cases, it is important to ascertain the presence of similar symptoms in contacts of the patient and local public health officials must be notified as one case may herald an outbreak. Given the continued threat of bioterrorism, the Centre for Disease Control Surveillance System in the United States must also be notified of any cases of botulism.
Williams, J H; Bester, L; Venter, L; Pretorius, D; Greyling, F
2011-12-01
Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay neutralisation test, confirming that this male had had concomitant barbiturate toxicity and botulism, and had succumbed to aspiration bronchopneumonia secondary to pharyngeal, laryngeal and oesophageal paralysis and oesophageal
Rani, Sarita; Ponmariappan, S; Sharma, Arti; Kamboj, D V; Jain, A K
2017-01-01
Clostridium botulinum is an obligate anaerobic, Gram positive bacterium that secretes extremely toxic substances known as botulinum neurotoxins (BoNTs) that cause serious paralytic illness called botulism. Based upon the serological properties, these neurotoxin have been classified into seven serotypes designated from A to G. Due to extreme toxicity of BoNTs, these neurotoxins have been designated as category A biowarfare agents. There is no commercial neutralizing antibody available for the treatment of botulism. Hence there is an urgent need to develop therapeutic intervention for prevention and cure of botulism within short period. BoNT antiserum injection is still the effective treatment. In the present study, the recombinant light chain of BoNT/E was successfully purified in soluble form. The purified rBoNT/E LC was used for the generation of polyclonal antibody in rabbit. In order to find out the neutralizing capacity of generated antisera, rabbit antiserum was incubated with 20 LD50 of botulinum neurotoxin type E for 1 hour at 37°C and then injected intraperitoneally (IP) into mice. Further in another set of experiments antiserum was administered in different ways that included administration of - antiserum and BoNT/E toxin simultaneously without preincubation, one after another at the same and different time points for its therapeutic ability. To find out cross neutralization capacity, rBoNT/E LC antiserum was pre-incubated with 5 LD50 of BoNT/A, BoNT/B, BoNT/F and then injected (IP) into mice. In all the cases mice were observed continuously for 96 hours. The results clearly indicate that developed polyclonal rabbit antiserum showed serotype specific neutralization of BoNT/E toxin only but not of BoNT/A, BoNT/B and BoNT/F. The developed antibodies will be used for preventive and therapeutic intervention of type 'E' botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Gil, Luciana A. F.; da Cunha, Carlos Eduardo P.; Moreira, Gustavo M. S. G.; Salvarani, Felipe M.; Assis, Ronnie A.; Lobato, Francisco Carlos F.; Mendonça, Marcelo; Dellagostin, Odir A.; Conceição, Fabricio R.
2013-01-01
Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC) are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB), a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH)3) developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH)3 developed a protective immune response against both BoNT/C (5 IU/mL) and BoNT/D (10 IU/mL), as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH)3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle. PMID:23936080
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On botulinum neurotoxin variability.
Montecucco, Cesare; Rasotto, Maria Berica
2015-01-06
The rapidly growing number of botulinum neurotoxin sequences poses the problem of the possible evolutionary significance of the variability of these superpotent neurotoxins for toxin-producing Clostridium species. To progress in the understanding of this remarkable phenomenon, we suggest that researchers should (i) abandon an anthropocentric view of these neurotoxins as human botulism-causing agents or as human therapeutics, (ii) begin to investigate in depth the role of botulinum neurotoxins in animal botulism in the wilderness, and (iii) devote large efforts to next-generation sequencing of soil samples to identify novel botulinum neurotoxins. In order to compare the fitness of the different toxins, we suggest that assays of all the steps from toxin production to animal death should be performed. Copyright © 2015 Montecucco and Rasotto.
Single-tube nested PCR assay for the detection of avian botulism in cecal contents of chickens.
Jang, Il; Lee, Jae-Il; Kwon, Yong-Kuk; Kang, Min-Su; Kim, Hye-Ryoung; Park, Ji-Young; Lee, Song-Hyun; Lee, Hee-Soo; Bae, You-Chan
2015-10-01
This paper describes a novel diagnostic method for the detection of avian botulism caused by Clostridium botulinum type C and C/D, using single-tube nested PCR assay. This assay was developed to overcome the disadvantages of bioassays used in experiments with mice. Three primer pairs including an antisense primer were designed to target the N-terminal of the toxin gene from C. botulinum types C and C/D. The specificity of the PCR assay was confirmed by using 33 bacterial strains and chicken cecal contents from farms that experienced botulism outbreaks. The detection limit for purified DNA was 1.1 fg/μl, and for bacterial spores was 4.3 spores/200 mg of cecal contents. While checking for specificity of the PCR assay, the reactions with the templates form C. botulinum type C and C/D which were tested became positive, but the rest of the reactions turned negative. However, the results for all clinical samples (n = 8) were positive. The PCR assay results for cecal samples obtained from 300 healthy chickens (150 Korean native chickens and 150 broilers) were all negative. This assay is rapid and straightforward and evades ethical issues associated with mouse bioassay. Moreover, it is more economical than real-time PCR. Copyright © 2015 Elsevier Ltd. All rights reserved.
Outbreak of Foodborne Botulism Associated with Improperly Jarred Pesto--Ohio and California, 2014.
Burke, Patrick; Needham, Michael; Jackson, Brendan R; Bokanyi, Rick; St Germain, Eric; Englender, Steven J
2016-02-26
On July 28, 2014, the Cincinnati Health Department was notified of suspected cases of foodborne botulism in two women admitted to the same hospital 12 days apart. Patient A had been treated for 12 days for suspected autoimmune disease. When patient B, the roommate of patient A, was evaluated at the same medical center for similar symptoms, it was learned that on July 13, patient A and patient B had shared a meal that included prepackaged pesto from a jar; clinicians suspected botulism and notified the local health department. The pesto had been purchased from company A's farm stand in San Clemente, California. Laboratory testing detected botulinum toxin type B by enzyme-linked immunosorbent assay (ELISA) in leftovers of pasta with pesto. A culture of these food samples yielded Clostridium spp. that produced botulinum toxin type B; polymerase chain reaction (PCR) testing also was positive for type B toxin gene. Environmental assessment of company A identified improper acidification and pressurization practices and lack of licensure to sell canned products commercially, including products in hermetically-sealed jars. On July 30, the vendor voluntarily recalled all jarred products, and the California Department of Public Health (CDPH) warned the public not to consume company A's jarred foods. This report describes the two cases and the public health investigation that traced the source of the outbreak.
Type C botulism in a commercial turkey farm: a case report.
Popp, Christina; Hauck, Rüdiger; Gad, Wael; Hafez, Hafez M
2012-12-01
Botulism is an intoxication caused by exotoxins of Clostridium botulinum. The case of botulism described here occurred on a commercial meat turkey farm with two houses. Toms and hens were maintained in two separate houses, toms in house A and hens in house B. At 10 wk of age, an increase in mortality was observed in the toms located in house A. Clinically the animals presented with paralysis of the legs, wings, and neck. Affected birds were sitting and reluctant to move. Necropsy failed to find any specific lesions. In liver, heart, muscles, crop, and gizzard as well as in intestinal contents, DNA of C. botulinum type C was detected by PCR. The result was confirmed by a mouse lethality neutralization test. During the 2 wk after the onset of the clinical signs the mortality was about 12%. The hens kept in house B did not show any symptoms and remained healthy. Investigations of environmental samples to detect the source of the toxin were not successful. After 2 wk clinical signs and mortality abated. At 16 wk of age, toms again showed the same clinical signs accompanied by raised mortality. Again C. botulinum toxin type C was detected. Within 2 wk the total mortality reached roughly 50%. Based on the "precautionary principle" and in agreement with the local authorities, the birds were euthanatized using CO2 in order to not compromise food safety.
Investigation of Clostridium botulinum group III's mobilome content.
Woudstra, Cédric; Le Maréchal, Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie-Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B; Lobato, Francisco C F; Silva, Rodrigo O S; Dorner, Martin B; Fach, Patrick
2018-02-01
Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C. botulinum group III were developed with the objective to better characterize C. botulinum group III strains. The investigation of 110 C. botulinum group III strains and 519 naturally contaminated samples collected during botulism outbreaks in Europe showed alpha-toxin and C2-I/C2-II markers to be systematically associated with type C/D bont-positive samples, which may indicate an important role of these elements in the pathogenicity mechanisms. On the contrary, bont type D/C strains and the related positive samples appeared to contain almost none of the markers tested. Interestingly, 31 bont-negative samples collected on farms after a botulism outbreak revealed to be positive for some of the genetic mobile elements tested. This suggests loss of the bont phage, either in farm environment after the outbreak or during laboratory handling. Copyright © 2017 Elsevier Ltd. All rights reserved.
Infantile botulism: clinical and laboratory observations of a rare neuroparalytic disease.
Urdaneta-Carruyo, E; Suranyi, A; Milano, M
2000-04-01
A 3-month-old male infant was admitted to the University Hospital of Los Andes with a history of constipation, weak crying, poor feeding, flaccidity and later bilateral ptosis and hyporeflexia. The admission diagnosis was septicaemia until an electrophysiological study reported postetanic facilitation with 50 Hz/seg stimulations four days later. The Clostridium botulinum toxin type B was isolated from the infant's stool samples and the organism grew in anaerobic cultures. The patient recovered completely and was discharged 2 months later. Although infant botulism is an uncommon disease in our environment, this diagnosis must be suspected in all afebrile infants with constipation, affected cranial nerves and generalized hypotonia. The principal differential diagnoses are Landry-Guillain-Barré syndrome, poliomyelitis, myasthenia gravis and infant muscular atrophy.
Lobotomies and Botulism Bombs: Beckett's Trilogy and the Cold War.
Piette, Adam
2016-06-01
The article argues that Beckett's Trilogy stages the effects of a lobotomy operation on a potentially politically subversive writer, and that the consequences of the operation can be traced in both the retreat of the narrator(s) of the Trilogy into the mind and into comatose mental states and in the detail of the operation itself, based on the 'icepick' lobotomies performed by neurologist Walter Freeman in the late 1940s and early 1950s. To write about extreme psychiatric situations in the post-war period is necessarily to invoke the political uses of psychosurgery with which this article engages. The article goes on to consider the figure of the brain-damaged mind as a Cold War trope in the references to botulism and the motif of the penetrated skull in The Unnamable.
... your child an intravenous antitoxin that blocks the activity of the toxin in his bloodstream. This can help ease symptoms when given early in the infectious process. Antibacterials are not helpful in treating most cases of ...
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Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques.
Kodihalli, Shantha; Emanuel, Andrew; Takla, Teresa; Hua, Yi; Hobbs, Charles; LeClaire, Ross; O'Donnell, Denise C
2017-01-01
There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques. In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher's exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher's exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease. A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication and subsequent death when administered as PEP treatment. These data in part supported the licensure of BAT under the Animal Rule in the United States by the Food and Drug Administration.
CSTE Botulism Surveillance Summary, 2014
... one with seal oil (3 cases), one with pasta and jarred pesto* (2 cases), and one with ... food Home-canned tomato sauce Homemade beef stew* Pasta and jarred pesto § Stinkheads Home-canned pickles* Home- ...
A case of type B botulism in a pregnant bitch.
Lamoureux, A; Pouzot-Nevoret, C; Escriou, C
2015-05-01
A two-year-old pregnant Gordon setter presented with acute onset of flaccid tetraparesis and respiratory distress. Neurological examination revealed diffuse lower motor neuron dysfunction. Clostridium botulinum neurotoxin B was isolated from the dog's serum. The dog was hospitalised and received supportive care; respiratory function was monitored but positive-pressure ventilation was not required. Recovery was complete within 1 month and parturition occurred without complication 49 days after admission. The puppies delivered lacked any obvious congenital defects and development during the first few months of life was normal. The source of contamination was suspected to be poorly conserved dry food. To the authors' knowledge, this is the first report of C. botulinum neurotoxin B isolation in a dog and the first report of botulism in a pregnant bitch. © 2014 British Small Animal Veterinary Association.
Avian botulism type E in waterbirds of Lake Michigan, 2010–2013
Chipault, Jennifer G.; White, C. LeAnn; Blehert, David S.; Jennings, Susan K.; Strom, Sean M.
2015-01-01
During 2010 to 2013, waterbird mortality surveillance programs used a shared protocol for shoreline walking surveys performed June to November at three areas in northern Lake Michigan. In 2010 and 2012, 1244 total carcasses (0.8 dead bird/km walked) and 2399 total carcasses (1.2 dead birds/km walked), respectively, were detected. Fewer carcasses were detected in 2011 (353 total carcasses, 0.2 dead bird/km walked) and 2013 (451 total carcasses, 0.3 dead bird/km walked). During 3 years, peak detection of carcasses occurred in October and involved primarily migratory diving and fish-eating birds, including long-tailed ducks (Clangula hyemalis; 2010), common loons (Gavia immer; 2012), and red-breasted mergansers (Mergus serrator; 2013). In 2011, peak detection of carcasses occurred in August and consisted primarily of summer residents such as gulls (Larus spp.) and double-crested cormorants (Phalacrocorax auritus). A subset of fresh carcasses was collected throughout each year of the study and tested for botulinum neurotoxin type E (BoNT/E). Sixty-one percent of carcasses (57/94) and 10 of 11 species collected throughout the sampling season tested positive for BoNT/E, suggesting avian botulism type E was a major cause of death for both resident and migratory birds in Lake Michigan. The variety of avian species affected by botulism type E throughout the summer and fall during all 4 years of coordinated surveillance also suggests multiple routes for bird exposure to BoNT/E in Lake Michigan.
Sensitivity of mouse bioassay in clinical wound botulism.
Wheeler, Charlotte; Inami, Gregory; Mohle-Boetani, Janet; Vugia, Duc
2009-06-15
California has an ongoing epidemic of wound botulism (WB) among injection drug users (IDUs). We retrospectively studied a cohort of patients with WB and determined the sensitivity of the mouse bioassay-the gold standard laboratory test for confirmation of botulism-in verifying WB. We defined a clinical case of WB as an acute, bilateral, descending, flaccid paralysis starting with 1 cranial nerve palsies in an IDU with no other explainable diagnosis. We calculated the sensitivity of the mouse bioassay as the proportion of clinical WB cases that had positive serum toxin test results by mouse bioassay. We compared serum toxin-positive with serum toxin-negative patients. Of 73 patients with WB, 50 tested serum toxin positive, yielding a sensitivity of 68%. Serum toxin-positive patients did not differ significantly from serum toxin-negative patients with respect to demographic characteristics or injection drug use practices or in days from patient symptom onset to collection of specimens for testing. Patients did not differ significantly by clinical characteristics, except that serum toxin-positive patients were more likely than serum toxin-negative patients to have required mechanical ventilation during their hospital courses (74% vs. 43%; P = .01). In this study, the mouse bioassay failed to detect botulinum toxin in the serum samples of nearly one-third of IDUs with characteristic WB. Such patients should be considered to have probable WB. Physicians should be aware of the test's limitations and base their final diagnosis of suspected WB on clinical criteria when the mouse bioassay produces negative results.
Fatal course of foodborne botulism in an eight-month old infant
Lonati, Davide; Locatelli, Carlo Alessandro; Fenicia, Lucia; Anniballi, Fabrizio; Landri, Paolo; Giampreti, Andrea; Petrolini, Valeria Margherita; Vecchio, Sarah; Manzo, Luigi
2011-01-01
An 8-month old girl, weighing 9 kg, was brought by her parents at 8.15 am to the Emergency Department (ED) for a progressive worsening of weakness and acute respiratory failure. On admission, the baby presented with poor oral intake, a weak cry and extremely weak muscular body control. Poor gag and suck, unreactive mydriasis, hypotonia, lethargy and absence of peristalsis were noted. Laboratory data showed severe respiratory acidosis. Chest X-ray, electroencephalography, encephalic CT scan and MRI were all normal, as were cerebrospinal fluid analysis and viral tests. Orotracheal intubation and continuous mechanical ventilation were applied. The patient received fluids, corticosteroids, aerosol therapy, large-spectrum antibiotics and enteral-nutrition. Further investigation revealed ingestion of an improperly prepared home-canned homogenized turkey meal. Type A botulinum neurotoxin was identified. Trivalent botulinum antitoxin, prostigmine and oral activated charcoal were administered. Generalized flaccid paralysis, areflexic bilateral mydriasis, gastric stasis and deep coma persisted for the duration of the hospital stay, and the patient died of severe respiratory failure and cardiac arrest 12 days after ED admission. Botulism poisoning should be suspected in any infant presenting with feeding difficulties, constipation, descendent paralysis or acute respiratory failure. Supportive treatment and antidotal therapy should be performed as soon as a clinical diagnosis is made. We describe a case of foodborne botulism in an 8-month old infant caused by ingestion of an improperly prepared home-canned homogenized turkey meal, representing the youngest fatal case reported in medical literature. PMID:22355516
Investigations into an Outbreak of Botulism Caused by Clostridium botulinum Type C/D in Laying Hens.
Skarin, Hanna; Lindgren, Ylva; Jansson, Désirée S
2015-06-01
This case report describes a recent botulism outbreak in commercial laying hens with a history of increased mortality and flaccid paralysis. Routine diagnostic gross examination and microscopy from seven hens were inconclusive, but botulinum neurotoxin (BoNT) in peripheral blood was neutralized with both type C and type D antitoxins in the mouse bioassay. During a farm visit, 10 additional hens from a 34-wk-old flock on the farm were selected for clinical examination and further sampling. Nine hens were observed in sternal recumbency, with flaccid paralysis of the neck, drooping wings and tail, inability to escape, and bilateral ptosis, and one hen showed nonspecific clinical signs. Samples from cecum and liver were collected, and the gene coding for BoNT was detected by PCR in all 10 cecal samples and in four of the liver samples. Clostridium botulinum mosaic type C/D was isolated from 5 out of 10 hens from either cecum or liver, and the isolates were subjected to pulsed-field gel electrophoresis subtyping. All five isolates produced the same banding pattern, which was identical or showed >90% similarity to isolates from three different outbreaks on broiler farms in Sweden and Denmark during the 2007-10 period. However, they were clearly distinguishable from the predominantly reported pulsotype associated with avian botulism outbreaks in Europe. The authors are unaware of any previous report of C. botulinum mosaic type C/D isolates from laying hens.
[Familial microepidemic of food-borne botulism in the Region of Madrid].
Jalda, D; Junco, A; Alvarez-Moreno, M; Rodero, I; Carneado-Ruiz, J
2016-07-01
Botulism is a syndrome caused by the toxin of the bacillus Clostridium botulinum. The toxin acts by blocking the presynaptic cholinergic endings of the neuromuscular junction and of the parasympathetic nervous system, and gives rise to a flaccid paralysis and parasympathetic failure. The most common way to catch the disease is by ingestion of the preformed toxin present in badly sterilised home-made preserves, although other mechanisms are also possible. Its incidence in Spain today is very low. We report the case of three members of a family living together who presented a clinical picture of food-borne botulism. The initial clinical symptoms showed a predilection for ocular paresis and for dysautonomic symptoms of little specificity, and the familial aggregation was the fundamental evidence that suggested the diagnosis. Later, the patients' state got worse and two of them presented involvement of the respiratory function and required a lengthy stay in the intensive care unit. After a period of convalescence the three patients recovered without any sequelae. Botulinum toxin was detected by bioassay in some food samples, which allowed the diagnosis to be categorised as confirmed. The familial microepidemic reported here is a case of predominantly ocular and dysautonomic involvement. Likewise, it illustrates several aspects that are typical of the disease: the suspected diagnosis in cohabiting patients who visit at the same time for a similar clinical picture, the characteristic complications of the process and its treatment, the laboratory diagnosis and its natural history towards resolution.
A Novel Surface Plasmon Resonance Biosensor for the Rapid Detection of Botulinum Neurotoxins
Patel, Kruti; Halevi, Shmuel; Melman, Paul; Schwartz, John; Cai, Shuowei; Singh, Bal Ram
2017-01-01
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD50 of 1–2 ng/kg body weight), cause fatal flaccid paralysis by blocking neurotransmitter release. The current gold standard detection method, the mouse-bioassay, often takes days to confirm botulism. Furthermore, there are no effective antidotes known to reverse the symptoms of botulism, and as a result, patients with severe botulism often require meticulous care during the prolonged paralytic illness. To combat potential bio-terrorism incidents of botulinum neurotoxins, their rapid detection is paramount. Surface plasmon resonance (SPR) is a very sensitive technique to examine bio-molecular interactions. The label-free, real-time analysis, with high sensitivity and low sample consumption makes this technology particularly suitable for detection of the toxin. In this study, we demonstrated the feasibility in an assay with a newly designed SPR instrument for the rapid detection of botulinum neurotoxins. The LOD (limit of detection) of the Newton Photonics (NP) SPR based assay is 6.76 pg/mL for Botulinum Neurotoxin type A Light Chain (BoNT/A LC). We established that the detection sensitivity of the system is comparable to the traditional mouse LD50 bioassay in BoNT/A using this SPR technology. PMID:28783115
New Elements To Consider When Modeling the Hazards Associated with Botulinum Neurotoxin in Food.
Ihekwaba, Adaoha E C; Mura, Ivan; Malakar, Pradeep K; Walshaw, John; Peck, Michael W; Barker, G C
2016-01-15
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction and causing a spectrum of diseases ranging from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential biowarfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanisms and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature that will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modeling could be extended to include these new elements. Ultimately, this can offer further contributions to risk assessments to support food safety decision making. Copyright © 2015 Ihekwaba et al.
Feeding Your 8- to 12-Month-Old
... cause botulism in babies. Do not give regular cow's milk until your baby is older than 12 months ... babies are ready to go from formula to cow's milk. If you're breastfeeding, you can continue beyond ...
2012-12-11
coordination. For example, it conducted joint vehicle inspection training for Pakistani Customs and Border Guard personnel at a US- Mexico border...biological material, including such hazards as: anthrax, botulism, cholera , Ebola virus hemorrhagic fever, E. coli, Plague, and smallpox 79
A bibliography of references to avian botulism
Allen, Jack E.; Wilson, Sonoma S.
1977-01-01
This bibliography, first compiled in 1970 in response to many requests for information on avian botulism, has been updated to include the literature published through 1975.In general, only articles dealing primarily with the avian disease are included, as opposed to those concerned with various aspects of the biology of Clostridium botulinum, either type C or type E. A few exceptions, such as Bengton’s report of the first isolation and description of the type C organism, are included for their historical interest. Progress reports and other administrative documents not available for distribution or request are excluded, as are textbook accounts, which are generally summaries of work published elsewhere.Although Mr. Allen and Mrs. Wilson have attempted to list every important reference, they make no claim to complete coverage of the published literature. The authors will be grateful to users of the bibliography who call attention to errors or omissions.
Wound botulism from heroin skin popping.
Davis, Larry E; King, Molly K
2008-11-01
Following the introduction of black tar heroin mainly from Mexico in the 1980s, cases of wound botulism dramatically increased in the western United States. Contamination with spores of Clostridium botulinum of black tar heroin occurs along the distribution line. The heating of heroin powder to solubilize it for subcutaneous injection ("skin popping") does not kill the spores. The spores germinate in an anaerobic tissue environment and release botulinum toxin type A or B. Unless skin abscesses are found in the patient, the clinical diagnosis is often challenging. Facilitation of the compound muscle action potential by repetitive nerve stimulation at 20 to 50 Hz is an important and rapid diagnostic test. Definite diagnosis is made by detection of botulinum toxin in serum or isolation of C botulinum from the abscess. Early treatment with equine ABE botulinum antitoxin obtained from the Centers for Disease Control and Prevention often shortens the time on a ventilator.
[Intussusception in infant with diagnostic botulism: A case report].
Spini, Roxana G; Ferraris, Verónica; Glasman, María P; Orofino, Guillermina; Casanovas, Alejandra; Debaisi, Gustavo
2015-10-01
Botulism is an important public health problem in Argentina. It is a potentially fatal disease, and its diagnosis may be difficult. There are rare presentation forms of the disease, such as acute abdomen. We present a 4-month baby with a 3-day constipation condition, associated with weakness and abnormal eating attitude in the last 12 hours. The baby presented preserved muscle tone, with no changes in sucking or deglutition according to the mother's observations. Altered sensorium and acute abdomen were found; the patient was entered into the operating room with presumptive diagnosis of intussusception, which was confirmed by pneumatic desinvagination. During hospitalization, the patient did not make good progress and presented weak cry, progressive hypotonia and respiratory failure requiring intensive care. Clostridium botulinum was isolated from the stool sample and botulinum toxin type A was isolated from serum. The patient was treated with equine botulinum toxin. Twenty five days after admission, he was totally recovered.
Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study.
Maselli, R A; Ellis, W; Mandler, R N; Sheikh, F; Senton, G; Knox, S; Salari-Namin, H; Agius, M; Wollmann, R L; Richman, D P
1997-10-01
Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness. Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases. Muscle biopsies showed variable signs of neurogenic atrophy. In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder. Mechanical ventilation was required in 5 patients. Half of the patients were treated with polyvalent antitoxiin. Prognosis was favorable, though recovery was slow. In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism. High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.
Is downer cow syndrome related to chronic botulism?
Rulff, R; Schrödl, W; Basiouni, S; Neuhaus, J; Krüger, M
2015-01-01
The present work was directed to investigate the relationship between Downer cow syndrome (DCS) and chronic botulism in dairy cattle. For this purpose, a total of 52 fresh calving downer cows and 206 apparently healthy cows at 14 dairy farms were investigated for Clostridium botulinum ABE and CD antibody levels, C. botulinum and botulinum neurotoxin in rumen fluids as well as in faeces. Results indicated that the downer cows had higher IgG titers for C. botulinum ABE and CD than the healthy cows. All tested rumen fluids were negative for BoNT and C. botulinum. BoNT/D, however, and C. botulinum type D spores were detected in faecal samples of healthy and downer cows in the selected farms. In conclusion, the presence of a significantly higher C. botulinum ABE and CD antibody levels in DCS cows than in the healthy animals suggests that chronic C. botulinum toxico-infection could be a predisposing factor for DCS.
Detection of disease outbreaks by the use of oral manifestations.
Torres-Urquidy, M H; Wallstrom, G; Schleyer, T K L
2009-01-01
Oral manifestations of diseases caused by bioterrorist agents could be a potential data source for biosurveillance. This study had the objectives of determining the oral manifestations of diseases caused by bioterrorist agents, measuring the prevalence of these manifestations in emergency department reports, and constructing and evaluating a detection algorithm based on them. We developed a software application to detect oral manifestations in free text and identified positive reports over three years of data. The normal frequency in reports for oral manifestations related to anthrax (including buccal ulcers-sore throat) was 7.46%. The frequency for tularemia was 6.91%. For botulism and smallpox, the frequencies were 0.55% and 0.23%. We simulated outbreaks for these bioterrorism diseases and evaluated the performance of our system. The detection algorithm performed better for smallpox and botulism than for anthrax and tularemia. We found that oral manifestations can be a valuable tool for biosurveillance.
Akbulut, D; Grant, K A; McLauchlin, J
2005-09-01
An upsurge in wound infections due to Clostridium botulinum and Clostridium tetani among users of illegal injected drugs (IDUs) occurred in the United Kingdom during 2003 and 2004. A real-time PCR assay was developed to detect a fragment of the neurotoxin gene of C. tetani (TeNT) and was used in conjunction with previously described assays for C. botulinum neurotoxin types A, B, and E (BoNTA, -B, and -E). The assays were sensitive, specific, rapid to perform, and applicable to investigating infections among IDUs using DNA extracted directly from wound tissue, as well as bacteria growing among mixed microflora in enrichment cultures and in pure culture on solid media. A combination of bioassay and PCR test results confirmed the clinical diagnosis in 10 of 25 cases of suspected botulism and two of five suspected cases of tetanus among IDUs. The PCR assays were in almost complete agreement with the conventional bioassays when considering results from different samples collected from the same patient. The replacement of bioassays by real-time PCR for the isolation and identification of both C. botulinum and C. tetani demonstrates a sensitivity and specificity similar to those of conventional approaches. However, the real-time PCR assays substantially improves the diagnostic process in terms of the speed of results and by the replacement of experimental animals. Recommendations are given for an improved strategy for the laboratory investigation of suspected wound botulism and tetanus among IDUs.
Cortical recovery of swallowing function in wound botulism
Teismann, Inga K; Steinstraeter, Olaf; Warnecke, Tobias; Zimmermann, Julian; Ringelstein, Erich B; Pantev, Christo; Dziewas, Rainer
2008-01-01
Background Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. Methods In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM). Results The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. Conclusion These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia. PMID:18462489
Kenow, Kevin P.; Houdek, Steven C.; Fara, Luke; Gray, Brian R.; Lubinski, Brian R.; Heard, Darryl J.; Meyer, Michael W.; Fox, Timothy J.; Kratt, Robert
2018-01-01
Common loons (Gavia immer) staging on the Great Lakes during fall migration are at risk to episodic outbreaks of type E botulism. Information on distribution, foraging patterns, and exposure routes of loons are needed for understanding the physical and ecological factors that contribute to avian botulism outbreaks. Aerial surveys were conducted to document the spatiotemporal distribution of common loons on Lake Michigan during falls 2011–2013. In addition, satellite telemetry and archival geolocator tags were used to determine the distribution and foraging patterns of individual common loons while using Lake Michigan during fall migration. Common loon distribution observed during aerial surveys and movements of individual radiomarked and/or geotagged loons suggest a seasonal pattern of use, with early fall use of Green Bay and northern Lake Michigan followed by a shift in distribution to southern Lake Michigan before moving on to wintering areas. Common loons tended to occupy offshore areas of Lake Michigan and, on average, spent the majority of daylight hours foraging. Dive depths were as deep as 60 m and dive characteristics suggested that loons were primarily foraging on benthic prey. A recent study concluded that round gobies (Neogobius melanostomus) are an important prey item of common loons and may be involved in transmission of botulinum neurotoxin type E. Loon distribution coincides with the distribution of dreissenid mussel biomass, an important food resource for round gobies. Our observations support speculation that energy transfer to higher trophic levels via gobies may occur in deep-water habitats, along with transfer of botulinum neurotoxin.
Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach
Thanongsaksrikul, Jeeraphong; Chaicumpa, Wanpen
2011-01-01
Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT) derived from heterologous species (immunized animal or mouse hybridoma) together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R) domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa) is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH) that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80%) to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP), the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme. PMID:22069720
Vidal, Dolors; Laguna, Celia; Díaz-Sánchez, Sandra; Sánchez, Sergio; Chicote, Álvaro; Florín, Máximo; Mateo, Rafael
2014-01-01
Due to the scarcity of water resources in the “Mancha Húmeda” Biosphere Reserve, the use of treated wastewater has been proposed as a solution for the conservation of natural threatened floodplain wetlands. In addition, wastewater treatment plants of many villages pour their effluent into nearby natural lakes. We hypothesized that certain avian pathogens present in wastewater may cause avian mortalities which would trigger avian botulism outbreaks. With the aim of testing our hypothesis, 24 locations distributed in three wetlands, two that receive wastewater effluents and one serving as a control, were monitored during a year. Sediment, water, water bird feces, and invertebrates were collected for the detection of putative avian pathogenic Escherichia coli (APEC), Salmonella spp., Clostridium perfringens type A, and Clostridium botulinum type C/D. Also, water and sediment physicochemical properties were determined. Overall, APEC, C. perfringens, and C. botulinum were significantly more prevalent in samples belonging to the wetlands which receive wastewater. The occurrence of a botulism outbreak in one of the studied wetlands coincided with high water temperatures and sediment 5-day biochemical oxygen demand (BOD5), a decrease in water redox potential, chlorophyll a, and sulfate levels, and an increase in water inorganic carbon levels. The presence of C. botulinum in bird feces before the onset of the outbreak indicates that carrier birds exist and highlights the risk of botulinum toxin production in their carcasses if they die by other causes such as bacterial diseases, which are more probable in wastewater wetlands. PMID:24795377
Zanetti, Giulia; Azarnia Tehran, Domenico; Pirazzini, Marcon; Binz, Thomas; Shone, Clifford C; Fillo, Silvia; Lista, Florigio; Rossetto, Ornella; Montecucco, Cesare
2015-12-01
Botulinum neurotoxins (BoNTs) form a growing family of metalloproteases with a unique specificity either for VAMP, SNAP25 or syntaxin. The BoNTs are grouped in seven different serotypes indicated by letters from A to G. These neurotoxins enter the cytosol of nerve terminals via a 100 kDa chain which binds to the presynaptic membrane and assists the translocation of a 50 kDa metalloprotease chain. These two chains are linked by a single disulfide bridge which plays an essential role during the entry of the metalloprotease chain in the cytosol, but thereafter it has to be reduced to free the proteolytic activity. Its reduction is mediated by thioredoxin which is continuously regenerated by its reductase. Here we show that inhibitors of thioredoxin reductase or of thioredoxin prevent the specific proteolysis of VAMP by the four VAMP-specific BoNTs: type B, D, F and G. These compounds are effective not only in primary cultures of neurons, but also in preventing the in vivo mouse limb neuroparalysis. In addition, one of these inhibitors, Ebselen, largely protects mice from the death caused by a systemic injection. Together with recent results obtained with BoNTs specific for SNAP25 and syntaxin, the present data demonstrate the essential role of the thioredoxin-thioredoxin reductase system in reducing the interchain disulfide during the nerve intoxication mechanism of all serotypes. Therefore its inhibitors should be considered for a possible use to prevent botulism and for treating infant botulism. Copyright © 2015 Elsevier Inc. All rights reserved.
The unusual history and the urological applications of botulinum neurotoxin.
Hanchanale, Vishwanath S; Rao, Amrith Raj; Martin, Francis L; Matanhelia, Shyam S
2010-01-01
Botulinum neurotoxin (BoNT) is probably the most potent biological toxin that can affect humans. Since its discovery by Justinus Kerner, BoNT has seen use in a wide range of cosmetic and non-cosmetic conditions such as cervical dystonia, cerebral palsy, migraines and hyperhidrosis. We tried to trace its history from its inception to its recent urological applications. Historical articles about botulinum toxin were reviewed and a Medline search was performed for its urological utility. We hereby present a brief review of historical aspects of BoNT and its applications in urology. In 1793, the first known outbreak of botulism occurred due to 'spoiled' sausage in Wildebad, Germany. The German physician and poet Justinus Kerner published the first accurate description of the clinical symptoms of botulism (sausage poison). He was also the first to mention its potential therapeutic applications. In urology, BoNT has been used in bladder and urethral lesions with varying degree of success. Recently, BoNT applications were explained for prostatic disorders. BoNT applications in urology are in the treatment of detrusor external sphincter dyssynergia, detrusor overactivity, detrusor underactivity, spastic conditions of the urethral sphincter, chronic prostate pain, interstitial cystitis, non-fibrotic bladder outflow obstruction (including benign prostatic hyperplasia) and acute urinary retention in women. Justinus Kerner is the godfather of botulism research. The role of BoNT in urology has evolved exponentially and it is widely used as an adjuvant in voiding dysfunction. In the future, its utility will broaden and guide the urologist in managing various urological disorders. Copyright © 2010 S. Karger AG, Basel.
Clinical findings and treatment of 30 cattle with botulism.
Braun, U; Feige, K; Schweizer, G; Pospischil, A
2005-04-02
The clinical signs, the results of haematological and biochemical analyses and the treatment of 30 cattle with botulism are described, and the signs of the 13 cattle that survived are compared with those of the 17 that were euthanased owing to the disease. The cattle originated from 11 farms that had experienced an outbreak of botulism. The most important clinical sign in all the cattle was a reduction in the strength of the tongue; excessive salivation and difficulty in swallowing were observed in 20 of the animals, and the ears of 15 of them drooped. In 21 of the cattle, reaction to pricking of the head and body with a hypodermic needle was either absent or slight. Twelve of the animals had an unsteady, slow, difficult gait, and nine were unable to stand. A significantly higher proportion of the cattle which were euthanased had marked changes in behaviour and condition, anorexia, severely reduced skin turgor, weak tongues, a low rectal temperature, a high heart rate and a low blood pH; 11 were euthanased immediately after a clinical examination and six were euthanased one to five days after the initiation of treatment because their condition had deteriorated. Thirteen of the animals were treated for three to 23 days and were healthy when they were discharged. The treatment consisted of an intravenous infusion of 10 to 20 litres of glucose saline per day and the daily administration of fresh ruminal juice. Follow-up by telephone several months later revealed that all 13 animals had recovered completely.
Raghunath, Arvind; Perez-Branguli, Francesc; Smith, Leonard; Dolly, J Oliver
2008-04-02
Advances in viral gene therapy have opened new possibilities for treating a range of motor neuron diseases, but these have not yet been translated into clinically applicable therapies because of difficulties in delivery to susceptible/damaged neurons, ambiguities in the identity of gene(s) implicated, and a paucity of means to quantify any physiological improvement. Most of these hurdles can be overcome by using the neuromuscular paralysis induced by botulinum neurotoxin type A (BoNT/A) as a prototype disease. Furthermore, because human botulism, occasionally fatal, causes prolonged muscle disablement as a result of the intraneuronal persistence of the toxin's SNAP-25 (S25)-cleaving protease, development of a genetic approach could lead to a potential treatment for this debilitating disease. Adeno-associated viral delivery of a cleavage-resistant S25 gene (S25-R198T) to chromaffin cells in vitro yielded exocytotically active S25-R198T that diminished subsequent blockade by BoNT/A of evoked catecholamine release. Evaluation in vivo, by administering this virus into rat spinal cord before injecting BoNT/A, showed a decreased inhibition of acetylcholine release as reflected in elevated retention of neuromuscular transmission. A similar, although smaller, protection of synaptic transmission from the toxin was seen after peripherally injecting the therapeutic virus. Such therapy also curtailed nerve sprouting normally induced by BoNT/A. This first demonstration of the utility of a DNA-based therapy for botulism paves the way for further advances in its treatment and for application to genetic disorders of motor neurons.
Cortical recovery of swallowing function in wound botulism.
Teismann, Inga K; Steinstraeter, Olaf; Warnecke, Tobias; Zimmermann, Julian; Ringelstein, Erich B; Pantev, Christo; Dziewas, Rainer
2008-05-07
Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM). The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.
The impact of disease in the American white pelican in North America
Rocke, Tonie E.; Converse, Kathryn A.; Meteyer, Carol U.; McLean, R.
2005-01-01
Records of reported die-offs of the American White Pelican (Pelicanus erythrorhynchos) held by the U.S. Geological Survey National Wildlife Health Center from 1978 through 2003 indicate that type C botulism (caused by Clostridium botulinum) was the major cause of mortality. In 1996, over 15,000 birds, including 8,500 American White Pelicans, were estimated to have died from type C botulism at the Salton Sea in California. This was the largest documented die-off of any pelican species and was estimated to represent 15-20% of the western metapopulation. This event was also notable in that it was the first time that fish, specifically Tilapia (Oreochromis mossambicus), were implicated as the source of type C botulinum toxin for birds. Type C botulism has recurred in both North American species of pelicans at the Salton Sea every year since, although the magnitude of mortality is much lower. West Nile virus caused mortality in both adult and immature American White Pelicans, but may have a more significant impact on nestlings. Emaciation and mortality is common in pelican nesting colonies. Further clarification of the cause of nestling mortality and the ability to differentiate background mortality from mortality due to infectious disease agents such as West Nile virus and Newcastle disease virus would be important in determining the impact of disease in pelicans. Although definitive conclusions cannot be drawn, the number of die-offs and the estimated losses of American White Pelicans appears to have increased along with declines in number in western U.S.
Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques
Emanuel, Andrew; Takla, Teresa; Hua, Yi; Hobbs, Charles; LeClaire, Ross; O’Donnell, Denise C.
2017-01-01
Background There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)—(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques. Methods and findings In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher’s exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher’s exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease. Conclusions A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication and subsequent death when administered as PEP treatment. These data in part supported the licensure of BAT under the Animal Rule in the United States by the Food and Drug Administration. PMID:29166654
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-07
... respirators, Respiratory support devices, Ventilators, Anthrax, Smallpox, Botulism, Acute radiation syndrome...] and Relenza[supreg] when used for pandemic purposes; (5) smallpox countermeasures; (6) acute radiation syndrome countermeasures; (7) pandemic influenza diagnostics, personal respiratory devices, and respiratory...
Characterization of Clostridium botulinum Type B Neurotoxin Associated with Infant Botulism in Japan
Kozaki, Shunji; Kamata, Yoichi; Nishiki, Tei-ichi; Kakinuma, Hiroaki; Maruyama, Hiromi; Takahashi, Hiroaki; Karasawa, Tadahiro; Yamakawa, Kiyotaka; Nakamura, Shinichi
1998-01-01
The neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a food-borne botulism-related strain, Okra. The specific toxicity of 111/NT was found to be about 10 times lower than that of Okra/NT. The monoclonal antibodies recognizing the light chain cross-reacted with both neurotoxins, whereas most of the antibodies recognizing the carboxyl-terminal half of the heavy chain of Okra/NT did not react to 111/NT. Binding experiments with rat brain synaptosomes revealed that 125I-labeled 111/NT bound to a single binding site with a dissociation constant (Kd) of 2.5 nM; the value was rather lower than that (0.42 nM) of 125I-Okra/NT for the high-affinity binding site. In the lipid vesicles reconstituted with ganglioside GT1b, 125I-Okra/NT interacted with the amino-terminal domain of synaptotagmin 1 (Stg1N) or synaptotagmin 2 (Stg2N), fused with the maltose-binding protein, in the same manner as the respective full-length synaptotagmins, and the Kd values accorded with those of the low- and high-affinity binding sites in synaptosomes. However, 125I-111/NT only exhibited a low capacity for binding to the lipid vesicles containing Stg2N, but not Stg1N, in the presence of ganglioside GT1b. Moreover, synaptobrevin-2, an intracellular target protein, was digested to the same extent by the light chains of both neurotoxins in a concentration-dependent manner. These findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity. PMID:9746583
Outcome of adult horses with botulism treated at a veterinary hospital: 92 cases (1989-2013).
Johnson, A L; McAdams-Gallagher, S C; Aceto, H
2015-01-01
There are no studies evaluating a large population of adult horses treated for botulism. Reported survival rates in outbreak situations are low; however, many horses in outbreaks do not receive treatment. That adult horses treated at a veterinary hospital would have improved survival compared to outbreak situations. Additional aims included identification of predictors of nonsurvival. All horses greater than 6 months of age with a final diagnosis of botulism admitted to a veterinary teaching hospital between 1989 and 2013 were included. Retrospective study. Historical, admission, and hospitalization data were retrieved from medical records and associations between variables and nonsurvival were identified using logistic regression. Two multivariable models were developed pertaining to (1) information available at admission and (2) clinical findings during hospitalization. Ninety-two records met inclusion criteria. Retained variables for the two models indicated that higher rectal temperature (OR, 1.94; CI, 1.19-3.17) and dysphagia (OR, 4.04; CI, 1.01-16.17) observed at admission increased the odds of survival, as did treatment with antitoxin (OR, 121.30; CI, 9.94-1,480.65). Horses with abnormal respiratory effort or inability to stand had decreased odds of survival. Overall survival was 48% but was significantly higher (67%, P = .011) for horses that arrived standing, and even higher (95%, P < .001) for horses that remained able to stand throughout hospitalization. Complications occurred in 62% of horses but were not associated with nonsurvival. Horses that lose the ability to stand have a poor chance of survival. Complications are common in treated horses but do not reduce survival. Copyright © 2014 by the American College of Veterinary Internal Medicine.
Sekizuka, Tsuyoshi; Yamamoto, Akihiko; Iwaki, Masaaki; Komiya, Takako; Hatakeyama, Takashi; Nakajima, Hiroshi; Takahashi, Motohide; Kuroda, Makoto; Shibayama, Keigo
2014-01-01
Genetic characterization was performed for 10 group I Clostridium botulinum strains isolated from botulism cases in Japan between 2006 and 2011. Of these, 1 was type A, 2 were type B, and 7 were type A(B) {carrying a silent bont/B [bont/(B)] gene} serotype strains, based on botulinum neurotoxin (BoNT) production. The type A strain harbored the subtype A1 BoNT gene (bont/A1), which is associated with the ha gene cluster. The type B strains carried bont/B5 or bont/B6 subtype genes. The type A(B) strains carried bont/A1 identical to that of type A(B) strain NCTC2916. However, bont/(B) genes in these strains showed single-nucleotide polymorphisms (SNPs) among strains. SNPs at 2 nucleotide positions of bont/(B) enabled classification of the type A(B) strains into 3 groups. Pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem-repeat analysis (MLVA) also provided consistent separation results. In addition, the type A(B) strains were separated into 2 lineages based on their plasmid profiles. One lineage carried a small plasmid (5.9 kb), and another harbored 21-kb plasmids. To obtain more detailed genetic information about the 10 strains, we sequenced their genomes and compared them with 13 group I C. botulinum genomes in a database using whole-genome SNP analysis. This analysis provided high-resolution strain discrimination and enabled us to generate a refined phylogenetic tree that provides effective traceability of botulism cases, as well as bioterrorism materials. In the phylogenetic tree, the subtype B6 strains, Okayama2011 and Osaka05, were distantly separated from the other strains, indicating genomic divergence of subtype B6 strains among group I strains. PMID:25192986
Bano, Luca; Drigo, Ilenia; Tonon, Elena; Berto, Giacomo; Tavella, Alexander; Woudstra, Cedric; Capello, Katia; Agnoletti, Fabrizio
2015-12-01
Bovine botulism is a sporadic acute disease that usually causes catastrophic losses in the herds. The unusual clinical evolution of a persistent mild outbreak in a dairy herd, prompted us to characterize the neurotoxin gene profile of the strain involved and to evaluate whether seroconversion had occurred. Diagnosis was based on mild classical symptoms and was supported by PCR and bacteriological findings, which revealed the involvement of a non-mosaic type C strain. An in-house ELISA was developed to detect antibodies to botulinum neurotoxin type C and its performance was evaluated in a vaccination study. Fifty days after the index case, fecal and serum samples were collected from the 14 animals of the herd and screened for Clostridium botulinum and anti-botulinum neurotoxin antibodies type C, respectively. The in-house developed ELISA was also used to test 100 sera samples randomly collected from 20 herds. Strong ELISA reactions were observed in 3 convalescent and 5 asymptomatic animals involved in the studied outbreak. The ELISA-positive cows all tested positive for non-mosaic C. botulinum type C in the feces and the same strain was also detected in the alfalfa hay, suspected to be the carrier source. Ten out of the 100 randomly collected sera tested positive for anti-botulinum neurotoxin type C antibodies: 7 had borderline values and 3 from the same herd showed titers three times higher than the cut-off. We concluded that type C botulism in cattle may occur with variable severity and that prolonged exposure to sublethal doses of botulinum neurotoxin C may occur, resulting in detectable antibodies. Copyright © 2015 Elsevier Ltd. All rights reserved.
Wangroongsarb, Piyada; Kohda, Tomoko; Jittaprasartsin, Chutima; Suthivarakom, Karun; Kamthalang, Thanitchi; Umeda, Kaoru; Sawanpanyalert, Pathom; Kozaki, Shunji; Ikuta, Kazuyoshi
2014-01-01
Background Thailand has had several foodborne outbreaks of botulism, one of the biggest being in 2006 when laboratory investigations identified the etiologic agent as Clostridium botulinum type A. Identification of the etiologic agent from outbreak samples is laborious using conventional microbiological methods and the neurotoxin mouse bioassay. Advances in molecular techniques have added enormous information regarding the etiology of outbreaks and characterization of isolates. We applied these methods in three outbreaks of botulism in Thailand in 2010. Methodology/Principal Findings A total of 19 cases were involved (seven each in Lampang and Saraburi and five in Maehongson provinces). The first outbreak in Lampang province in April 2010 was associated with C. botulinum type F, which was detected by conventional methods. Outbreaks in Saraburi and Maehongson provinces occurred in May and December were due to C. botulinum type A1(B) and B that were identified by conventional methods and molecular techniques, respectively. The result of phylogenetic sequence analysis showed that C. botulinum type A1(B) strain Saraburi 2010 was close to strain Iwate 2007. Molecular analysis of the third outbreak in Maehongson province showed C. botulinum type B8, which was different from B1–B7 subtype. The nontoxic component genes of strain Maehongson 2010 revealed that ha33, ha17 and botR genes were close to strain Okra (B1) while ha70 and ntnh genes were close to strain 111 (B2). Conclusion/Significance This study demonstrates the utility of molecular genotyping of C. botulinum and how it contributes to our understanding the epidemiology and variation of boNT gene. Thus, the recent botulism outbreaks in Thailand were induced by various C. botulinum types. PMID:24475015
Application of PCR to a clinical and environmental investigation of a case of equine botulism.
Szabo, E A; Pemberton, J M; Gibson, A M; Thomas, R J; Pascoe, R R; Desmarchelier, P M
1994-08-01
PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostridium botulinum type B was shown to be prevalent in soils collected from the area in which the foal was raised. Four methods were used to test for the presence of botulinum neurotoxin-producing organisms in 66 soil samples taken within a 5-km radius: PCR and agarose gel electrophoresis (types A to E), PCR and an enzyme-linked assay (type B), hybridization of crude alkaline cell lysates with a type B-specific probe, and the mouse bioassay (all types). Fewer soil samples were positive for C. botulinum type B by the mouse bioassay (15%) than by any of the DNA-based detection systems. Hybridization of a type B-specific probe to DNA dot blots (26% of the samples were positive) and PCR-enzyme-linked assay (77% of the samples were positive) were used for the rapid analysis of large numbers of samples, with sensitivity limits of 3 x 10(6) and 3,000 cells, respectively. Conventional detection of PCR products by gel electrophoresis was the most sensitive method (300-cell limit), and in the present environmental survey, neurotoxin B genes only were detected in 94% of the samples.
Wangroongsarb, Piyada; Kohda, Tomoko; Jittaprasartsin, Chutima; Suthivarakom, Karun; Kamthalang, Thanitchi; Umeda, Kaoru; Sawanpanyalert, Pathom; Kozaki, Shunji; Ikuta, Kazuyoshi
2014-01-01
Thailand has had several foodborne outbreaks of botulism, one of the biggest being in 2006 when laboratory investigations identified the etiologic agent as Clostridium botulinum type A. Identification of the etiologic agent from outbreak samples is laborious using conventional microbiological methods and the neurotoxin mouse bioassay. Advances in molecular techniques have added enormous information regarding the etiology of outbreaks and characterization of isolates. We applied these methods in three outbreaks of botulism in Thailand in 2010. A total of 19 cases were involved (seven each in Lampang and Saraburi and five in Maehongson provinces). The first outbreak in Lampang province in April 2010 was associated with C. botulinum type F, which was detected by conventional methods. Outbreaks in Saraburi and Maehongson provinces occurred in May and December were due to C. botulinum type A1(B) and B that were identified by conventional methods and molecular techniques, respectively. The result of phylogenetic sequence analysis showed that C. botulinum type A1(B) strain Saraburi 2010 was close to strain Iwate 2007. Molecular analysis of the third outbreak in Maehongson province showed C. botulinum type B8, which was different from B1-B7 subtype. The nontoxic component genes of strain Maehongson 2010 revealed that ha33, ha17 and botR genes were close to strain Okra (B1) while ha70 and ntnh genes were close to strain 111 (B2). This study demonstrates the utility of molecular genotyping of C. botulinum and how it contributes to our understanding the epidemiology and variation of boNT gene. Thus, the recent botulism outbreaks in Thailand were induced by various C. botulinum types.
Application of PCR to a clinical and environmental investigation of a case of equine botulism.
Szabo, E A; Pemberton, J M; Gibson, A M; Thomas, R J; Pascoe, R R; Desmarchelier, P M
1994-01-01
PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostridium botulinum type B was shown to be prevalent in soils collected from the area in which the foal was raised. Four methods were used to test for the presence of botulinum neurotoxin-producing organisms in 66 soil samples taken within a 5-km radius: PCR and agarose gel electrophoresis (types A to E), PCR and an enzyme-linked assay (type B), hybridization of crude alkaline cell lysates with a type B-specific probe, and the mouse bioassay (all types). Fewer soil samples were positive for C. botulinum type B by the mouse bioassay (15%) than by any of the DNA-based detection systems. Hybridization of a type B-specific probe to DNA dot blots (26% of the samples were positive) and PCR-enzyme-linked assay (77% of the samples were positive) were used for the rapid analysis of large numbers of samples, with sensitivity limits of 3 x 10(6) and 3,000 cells, respectively. Conventional detection of PCR products by gel electrophoresis was the most sensitive method (300-cell limit), and in the present environmental survey, neurotoxin B genes only were detected in 94% of the samples. Images PMID:7989554
Mazuet, Christelle; Legeay, Christine; Sautereau, Jean; Bouchier, Christiane; Criscuolo, Alexis; Bouvet, Philippe; Trehard, Hélène; Jourdan Da Silva, Nathalie; Popoff, Michel
2017-02-01
A second botulism outbreak due to Clostridium baratii occurred in France in August 2015 and included three patients who had their meal in a restaurant the same day. We report the characterization of C. baratii isolates including whole genome sequencing (WGS). Four C. baratii isolates collected in August 2015 from the outbreak 2 were analysed for toxin production and typing as well as for genetic characterization. WGS was done using using the NEBNext Ultra DNA Library Prep kit for Illumina (New England Biolabs) and sequenced on MiSeq machine (Illumina) in paired-end reads of 250 bases. The phylogenetic tree was generated based on the UPGMA method with genetic distances computed by using the Kimura two-parameter model. Evolutionary analyses were conducted in Bionumerics (V.6.6 Applied Maths). Three C. baratii isolates for patient's stools and one isolate from meat produced botulinum neurotoxin (BoNT) type F and retained a bont/F7 gene in OrfX cluster. All isolates were identical according to the WGS. However, phylogeny of the core genome showed that the four C. baratii strains were distantly related to that of the previous C. baratii outbreak in France in 2014 and from the other C. baratii strains reported in databanks. The fact that the strains isolated from the patients and meat samples were genetically identical supports that the meat used for the Bolognese sauce was responsible for this second botulism outbreak in France. These isolates were unrelated to that from the first C. baratii outbreak in France in 2014 indicating a distinct source of contamination. WGS provided robust determination of genetic relatedness and information regarding BoNT typing and toxin gene locus genomic localization.
Ability of physicians to diagnose and manage illness due to category A bioterrorism agents.
Cosgrove, Sara E; Perl, Trish M; Song, Xiaoyan; Sisson, Stephen D
2005-09-26
Early recognition of a terrorist attack with biologic agents will rely on physician diagnosis. Physicians' ability to diagnose and care for patients presenting after a bioterror event is unknown. The role of online case-based didactics to measure and improve knowledge in the diagnosis and treatment of these patients is unknown. A multicenter online educational intervention was completed by 631 physicians at 30 internal medicine residency programs in 16 states and Washington, DC, between July 1, 2003, and June 10, 2004. Participants completed a pretest, assessing ability to diagnose and manage potential cases of smallpox, anthrax, botulism, and plague. A didactic module reviewing diagnosis and management of these diseases was then completed, followed by a posttest. Pretest performance measured baseline knowledge. Posttest performance compared with pretest performance measured effectiveness of the educational intervention. Results were compared based on year of training and geographic location of the residency program. Correct diagnoses of diseases due to bioterrorism agents were as follows: smallpox, 50.7%; anthrax, 70.5%; botulism, 49.6%; and plague, 16.3% (average, 46.8%). Correct diagnosis averaged 79.0% after completing the didactic module (P<.001). Correct management of smallpox was 14.6%; anthrax, 17.0%; botulism, 60.2%; and plague, 9.7% (average, 25.4%). Correct management averaged 79.1% after completing the didactic module (P<.001). Performance did not differ based on year of training (P = .54) or geographic location (P = .64). Attending physicians performed better than residents (P<.001). Physician diagnosis and management of diseases caused by bioterrorism agents is poor. An online didactic module may improve diagnosis and management of diseases caused by these agents.
Therapeutic Approaches to the Treatment of Botulism
1989-10-01
of the clostridial neurotoxins (last report). It must now be reported that there is another unusual quality to the data on interactions. As just...636-640, 1986. Matsuoka, I., Syuto, B., Kurihara, K. and Kubo, S.: ADP- ribosylation of specific membrane proteins in pheochromocytoma and primary
Šilhár, Peter; Silvaggi, Nicholas R; Pellett, Sabine; Čapková, Kateřina; Johnson, Eric A; Allen, Karen N; Janda, Kim D
2013-03-01
Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a series of hydroxamates derived from 1-adamantylacetohydroxamic acid (3a) were prepared. From this group of compounds, an improved potency of about 17-fold was observed for two derivatives. Detailed mechanistic studies on these structures revealed a competitive inhibition model, with a K(i)=27 nM, which makes these compounds some of the most potent small molecule, non-peptidic BoNT/A LC inhibitors reported to date. Copyright © 2012 Elsevier Ltd. All rights reserved.
Cargo-Delivery Platforms for Targeted Delivery of Inhibitor Cargos Against Botulism
Wilson, Brenda A.; Ho, Mengfei
2015-01-01
Delivering therapeutic cargos to specific cell types in vivo poses many technical challenges. There is currently a plethora of drug leads and therapies against numerous diseases, ranging from small molecule compounds to nucleic acids to peptides to proteins with varying binding or enzymatic functions. Many of these candidate therapies have documented potential for mitigating or reversing disease symptoms, if only a means for gaining access to the intracellular target were available. Recent advances in our understanding of the biology of cellular uptake and transport processes and the mode of action of bacterial protein toxins have accelerated the development of toxin-based cargo-delivery vehicle platforms. This review provides an updated survey of the status of available platforms for targeted delivery of therapeutic cargos, outlining various strategies that have been used to deliver different types of cargo into cells. Particular emphasis is placed on the application of toxin-based approaches, examining critical issues that have hampered realization of post-intoxication antitoxins against botulism. PMID:25335885
Cargo-delivery platforms for targeted delivery of inhibitor cargos against botulism.
Wilson, Brenda A; Ho, Mengfei
2014-01-01
Delivering therapeutic cargos to specific cell types in vivo poses many technical challenges. There is currently a plethora of drug leads and therapies against numerous diseases, ranging from small molecule compounds to nucleic acids to peptides to proteins with varying binding or enzymatic functions. Many of these candidate therapies have documented potential for mitigating or reversing disease symptoms, if only a means for gaining access to the intracellular target were available. Recent advances in our understanding of the biology of cellular uptake and transport processes and the mode of action of bacterial protein toxins have accelerated the development of toxin-based cargo-delivery vehicle platforms. This review provides an updated survey of the status of available platforms for targeted delivery of therapeutic cargos, outlining various strategies that have been used to deliver different types of cargo into cells. Particular emphasis is placed on the application of toxin-based approaches, examining critical issues that have hampered realization of post-intoxication antitoxins against botulism.
[Three infants with constipation and muscular weakness: infantile botulism].
Thomasse, Y; Arends, J P; van der Heide, P A; Smit, L M E; van Weerden, T W; Fock, J M
2005-04-09
Two previously healthy infants, a boy of 10 weeks and a girl of 4 months presented with apathy and muscle weakness. A third previously healthy child, a girl of 6 weeks old was admitted with respiratory insufficiency. None of the three had had a bowel movement for a number of days. After extensive investigations which revealed few abnormalities Clostridium botulinum toxin was obtained in serum from all three children. Type-B-toxin was shown in the faeces of the older girl and boy; both recovered quickly. The other girl had type-A toxin; she died. Two of the three children were given honey to comfort them. Infantile botulism must be considered in every infant with symptoms of constipation and hypotonia. The diagnosis can quickly be confirmed by electromyography with repetitive 50-Hz-stimulation. Honey is a well-known source of the C. botulinum spore and should not be given to children under the age of 12 months. These three children are the first cases to be described in the Netherlands.
Botulism outbreak associated with poultry litter consumption in three Brazilian cattle herds.
Ortolani, E L; Brito, L A; Mori, C S; Schalch, U; Pacheco, J; Baldacci, L
1997-04-01
One hundred fifty-five of 201 cattle from 3 different farms showed clinical signs and died of botulism after eating the same batch of poultry litter contaminated with poultry and rodent carcasses. The cattle had access to poultry litter for only 1 d; afterwards it was removed from the diet. Death occurred over a period of 17 d after the poultry litter intake. The peak mortality was on day 4; 20 animals died within 10 d of the ingestion. The greater the intake of poultry litter, the higher the cattle mortality. Three steers which died on the first day had peracute effects while the remaining cattle showed classical signs. Twenty-five of the 46 surviving cattle had mild clinical signs, but recovered in a few days. Type C Clostridium botulinum toxin was found in extracts of the poultry litter, carcasses and cattle intestinal contents. Nutrient composition of the poultry litter was normal but pH was lower (6.9) than usual (7.5 to 9.3).
Botulinum neurotoxin serotypes detected by electrochemical impedance spectroscopy.
Savage, Alison C; Buckley, Nicholas; Halliwell, Jennifer; Gwenin, Christopher
2015-05-06
Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A-E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins.
Botulinum Neurotoxin Serotypes Detected by Electrochemical Impedance Spectroscopy
Savage, Alison C.; Buckley, Nicholas; Halliwell, Jennifer; Gwenin, Christopher
2015-01-01
Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A–E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins. PMID:25954998
BOTOX and our tax dollars at work
USDA-ARS?s Scientific Manuscript database
This seminar is intended for Masters level graduate students in biology at the University of the Pacific. Topics of the seminar will include information on USDA-ARS research at the Albany location and general background on botulism and neurotoxin biology. In addition, the following FCR unit botulinu...
Therapeutic Approaches to the Treatment of Botulism
1987-10-01
dependence of various preparations of type C toxin. An absence of toxin-induced pa alysis, or an unusually long time for onset of paralysis, at low...Kurihara, K. and Kubo, S.: ADP- ribosylation of specific membrane proteins in pheochromocytoma and primary-cultured brain cells by botulinum neurotoxins
Botulinum neurotoxin detection methods for public health response and surveillance
USDA-ARS?s Scientific Manuscript database
A single suspected case of foodborne botulism caused by food contaminated with botulinum neurotoxin (BoNTs) could evoke public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns...
[Clinical analysis of 53 patients with Clostridium botulinum food poisoning].
Zhang, Peng; Dong, Jianguang; Bai, Lili; Qiu, Zewu
2017-05-01
To analyze the epidemiologic data of patients with Clostridium botulinum food poisoning, and to improve the understanding, diagnosis and treatment of food borne botulism. A retrospective study was conducted. Fifty-three patients with Clostridium botulinum food poisoning admitted to Chinese PLA Center of Poisoning and Treatment from January 2009 to December 2016 were enrolled, and they were divided into mild, moderate, and severe groups according to the severity of disease. The clinical data including medical history, epidemiology data, routine blood test and blood biochemistry at hospital admission, the vital signs and arterial blood gas analysis before and after treatment, as well as the occurrence frequency of symptom and sign on set were collected. Fifty-three patients with food borne botulism were enrolled, with 33 patients in mild group, 13 in moderate group, and 7 in severe group. Most of the patients were female, the age distribution was in large span, the outbreak of disease was in groups mainly with the family, and patients were mainly located in Hebei Province, Beijing and Henan Province. The outbreaks were mainly happened in Spring and Summer, and homemade fermentation products were still the first cause of poisoning with the average latent period of (51.01±4.78) hours. The majority of patients with botulism were in mild resulted from the type A toxin. With the aggravation of disease, hospitalization time was gradually increased, white blood cell (WBC) and neutrophils (NEUT) at hospitalization admission, and respiratory rate (RR), heart rate (HR), fraction of inspired oxygen (FiO 2 ) before the treatment were shown in obviously rising trend, albumin (ALB) at hospitalization admission and pH, arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO 2 ) before treatment were in decline. The parameters in severe group were most severe, and had significant differences as compared with those of mild group [hospitalization time (days): 72.57±39.52 vs. 6.61±3.72, WBC (×10 9 /L): 13.01±6.44 vs. 6.85±2.07, NEUT: 0.85±0.07 vs. 0.63±0.14, RR (bpm): 32.14±4.33 vs. 15.18±1.70, HR (bpm): 132.29±5.19 vs. 75.54±8.24, FiO 2 : 0.32±0.05 vs. 0.21±0.00, ALB (g/L): 38.57±4.65 vs. 42.09±4.57, pH: 7.08±0.10 vs. 7.38±0.07, PaO 2 (mmHg, 1 mmHg = 0.133 kPa): 75.16±5.24 vs. 98.39±1.50, SaO 2 : 0.78±0.06 vs. 0.97±0.02, all P < 0.05]. The symptom and sign on set of 53 patients with food borne botulism was dizziness, followed by fatigue, blurred vision, nausea, and other symptoms and signs were lower than 50%, and the occurrence of dizziness with rank one happen rate was significantly higher than blurred vision and nausea (χ 2 values were 7.209 and 10.502 respectively, and P values were 0.007 and 0.004 respectively). After the on time prescription of botulinum antitoxins treatment, the clinical symptoms of patients could be relived quickly. All the patients were discharged without deaths. In order to improve the recovery of the food borne botulism poisoning patients, adequate antitoxin and the related organ supports should be prescribed on time.
2015-02-05
botulism or tetanus , whole-cell patch clamp electrophysiology was used to quantify spontaneous miniature excitory post-synaptic currents (mEPSCs) in...ESNs exposed to tetanus neurotoxin (TeNT) or botulinum neurotoxin (BoNT) serotypes / A-/G. In all cases, ESNs exhibited near-complete loss of synaptic
1990-12-01
Name Species Cover Mudflat Area Cocklebur Xanthium strumarium ង to ɝ Shepherd’s purse Capsella bursa pastoris Barnyard grass Echinochloa crusgalli...Lythrium salicaria Rice cutgrass Leersia oryzoides * Cocklebur Xanthium strumarium Love giais Era grostis hypnoides Bog rush Juncus sp. Aster Aster pilosus
USDA-ARS?s Scientific Manuscript database
Botulinum neurotoxins (BoNTs) are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins (NAPs). The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presenc...
Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization
USDA-ARS?s Scientific Manuscript database
Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. Therefore, there is...
Neurotoxicoses of small animals
DOE Office of Scientific and Technical Information (OSTI.GOV)
Simpson, S.T.
1976-02-01
Among the great variety of potentially neurotoxic substances are insecticides, rodenticides, herbicides, fungicides, heavy metals, plants, drugs, reptile and insect venoms, industrial chemicals and contaminated foodstuffs. The neurotoxicoses associated with several of these are described. Of the insecticides, organophosphates and chlorinated hydrocarbons are discussed. The heavy metals thallium and lead are discussed along with botulism and polyradiculoneuritis. 22 references.
Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera
USDA-ARS?s Scientific Manuscript database
The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...
Inhibiting oral intoxication of botulinum neurotoxin A by carbohydrate receptor mimics
USDA-ARS?s Scientific Manuscript database
Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes of BoNT intoxication, where BoNT assembles with several auxiliary proteins to surviv...
... from being sickened by microorganisms such as Salmonella , E. coli O157:H7 , and C. botulinum , which causes botulism. Keeping foods chilled at proper temperatures is one of the best ways to prevent or slow the growth of these ... | Tiếng Viá»t | íêµì´ | ...
Maslanka, Susan E.; Lúquez, Carolina; Dykes, Janet K.; Tepp, William H.; Pier, Christina L.; Pellett, Sabine; Raphael, Brian H.; Kalb, Suzanne R.; Barr, John R.; Rao, Agam; Johnson, Eric A.
2016-01-01
Botulism is a potentially fatal paralytic disease caused by the action of botulinum neurotoxin (BoNT) on nerve cells. There are 7 known serotypes (A–G) of BoNT and up to 40 genetic variants. Clostridium botulinum strain IBCA10-7060 was recently reported to produce BoNT serotype B (BoNT/B) and a novel BoNT, designated as BoNT/H. The BoNT gene (bont) sequence of BoNT/H was compared to known bont sequences. Genetic analysis suggested that BoNT/H has a hybrid-like structure containing regions of similarity to the structures of BoNT/A1 and BoNT/F5. This novel BoNT was serologically characterized by the mouse neutralization assay and a neuronal cell–based assay. The toxic effects of this hybrid-like BoNT were completely eliminated by existing serotype A antitoxins, including those contained in multivalent therapeutic antitoxin products that are the mainstay of human botulism treatment. PMID:26068781
Ruwona, Tinashe B; Xu, Haiyue; Li, Junwei; Diaz-Arévalo, Diana; Kumar, Amit; Zeng, Mingtao; Cui, Zhengrong
2016-05-03
Botulinum neurotoxin (BoNT) is a lethal neurotoxin, for which there is currently not an approved vaccine. Recent efforts in developing vaccine candidates against botulism have been directed at the heavy chain fragment of BoNT, because antibodies against this region have been shown to prevent BoNT from binding to its receptor and thus to nerve cell surface, offering protection against BoNT intoxication. In the present study, it was shown that immunization with plasmid DNA that encodes the 50 KDa C-terminal fragment of the heavy chain of BoNT serotype C (i.e., BoNT/C-Hc50) and is carried by cationic poly (lactic-co-glycolic) acid (PLGA) nanoparticles induces stronger BoNT/C-specific antibody responses, as compared to immunization with the plasmid alone. Importantly, the antibodies have BoNT/C-neutralizing activity, protecting the immunized mice from a lethal dose of BoNT/C challenge. A plasmid DNA vaccine encoding the Hc50 fragments of BoNT serotypes that cause human botulism may represent a viable vaccine candidate for protecting against botulinum neurotoxin intoxication.
Anza, Ibone; Skarin, Hanna; Vidal, Dolors; Lindberg, Anna; Båverud, Viveca; Mateo, Rafael
2014-04-01
Avian botulism is a paralytic disease caused by Clostridium botulinum-produced botulinum neurotoxins (BoNTs), most commonly of type C/D. It is a serious disease of waterbirds and poultry flocks in many countries in Europe. The objective of this study was to compare the genetic relatedness of avian C. botulinum strains isolated in Spain with strains isolated in Sweden using pulsed-field gel electrophoresis (PFGE). Fifteen strains were isolated from Spanish waterbirds using an immunomagnetic separation technique. Isolates were characterized by PCR, and all were identified as the genospecies Clostridium novyi sensu lato and eight harboured the gene coding for the BoNT type C/D. PFGE analysis of the strains revealed four highly similar pulsotypes, out of which two contained strains from both countries. It also showed that outbreaks in wild and domestic birds can be caused by the same strains. These results support a clonal spreading of the mosaic C. botulinum type C/D through Europe and give relevant information for future epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.
[Botulinum toxin--the dose controls the poison. A historical sketch].
Homann, C N; Wenzel, K; Kriechbaum, N; Suppan, K; Crevenna, R; Ivanic, G; Dressler, D
2002-06-01
Botulism, a potentially lethal form of paralytic food poisoning, was described as early as 1793. Basic research, especially in the late nineteenth and early twentieth centuries, revealed that botulism is caused by exotoxins. Further biochemical work around and after the Second World War gave insight into the molecular structure of seven different serotypes of botulinum toxin (BT/A-G) as well as into its acetylcholine blocking mode of action. In 1977, Scott treated patients with strabism by injecting minute amounts of purified BT/A. In short sequence, BT proved effective in blepharospasm, cervical dystonia, and various off-label indications. In the near future, registration of these new indications, marketing of new serotypes (BT/B), and availability of more practical antibody tests can be expected. The first applications of BT were performed by Roggenkaemper, Dressler, and Benecke in Germany and by Poewe and Auff in Austria. According to a worldwide trend, a rapid expansion regarding BT users and indications followed. Formation of BT competence centers in both countries aims at maintaining high standards in BT research and education.
Kalb, Suzanne R; Barr, John R
2013-08-01
Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.
Effects of botulinum toxin on strength-duration properties.
Yerdelen, Deniz; Koc, Filiz; Sarica, Yakup
2007-10-01
Axonal excitability studies have been used in several diseases to investigate the underlying pathophysiology. The threshold tracking technique was developed to measure noninvasively several indices of axonal excitability, such as strength-duration properties. This study investigated the possible effects of botulinum toxin on strength-duration time constant (SDTC) in patients with the symptoms and signs of botulism. The clinical and electrophysiological findings of 13 patients who were admitted to the authors' clinic with botulism signs and symptoms were evaluated in a 5-day period after exposure to the toxin prospectively. After routine diagnostic electroneuromyographic examinations and electromyogram with repetitive nerve stimulation at 20-50 Hz, SDTC was studied. The results were compared with 13 age- and sex-matched healthy volunteers. The SDTCs were 381 +/- 60 micros and 471 +/- 84 micros in patients and controls, respectively. There was a statistical difference between the two groups (p = .003, Mann Whitney U test). These findings suggest a possible effect of botulinum toxin, known to be effective at neuromuscular junction, on Na(+)/K(+) pump activity, and Na(+) or K(+) conductance.
Franciosa, Giovanna; Scalfaro, Concetta; Di Bonito, Paola; Vitale, Marco; Aureli, Paolo
2011-01-01
Since the first isolation of type E botulinum toxin-producing Clostridium butyricum from two infant botulism cases in Italy in 1984, this peculiar microorganism has been implicated in different forms of botulism worldwide. By applying particular pulsed-field gel electrophoresis run conditions, we were able to show for the first time that ten neurotoxigenic C. butyricum type E strains originated from Italy and China have linear megaplasmids in their genomes. At least four different megaplasmid sizes were identified among the ten neurotoxigenic C. butyricum type E strains. Each isolate displayed a single sized megaplasmid that was shown to possess a linear structure by ATP-dependent exonuclease digestion. Some of the neurotoxigenic C. butyricum type E strains possessed additional smaller circular plasmids. In order to investigate the genetic content of the newly identified megaplasmids, selected gene probes were designed and used in Southern hybridization experiments. Our results revealed that the type E botulinum neurotoxin gene was chromosome-located in all neurotoxigenic C. butyricum type E strains. Similar results were obtained with the 16S rRNA, the tetracycline tet(P) and the lincomycin resistance protein lmrB gene probes. A specific mobA gene probe only hybridized to the smaller plasmids of the Italian C. butyricum type E strains. Of note, a ß-lactamase gene probe hybridized to the megaplasmids of eight neurotoxigenic C. butyricum type E strains, of which seven from clinical sources and the remaining one from a food implicated in foodborne botulism, whereas this ß-lactam antibiotic resistance gene was absent form the megaplasmids of the two soil strains examined. The widespread occurrence among C. butyricum type E strains associated to human disease of linear megaplasmids harboring an antibiotic resistance gene strongly suggests that the megaplasmids could have played an important role in the emergence of C. butyricum type E as a human pathogen. PMID:21738770
Lévêque, Christian; Ferracci, Géraldine; Maulet, Yves; Mazuet, Christelle; Popoff, Michel; Seagar, Michael; El Far, Oussama
2014-07-15
Botulinum neurotoxin A (BoNT/A) has intrinsic endoprotease activity specific for SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation of SNAP-25 by BoNT/A underlies botulism, a rare but potentially fatal disease. There is a crucial need for a rapid and sensitive in vitro serological test for BoNT/A to replace the current in vivo mouse bioassay. Cleavage of SNAP-25 by BoNT/A generates neo-epitopes which can be detected by binding of a monoclonal antibody (mAb10F12) and thus measured by surface plasmon resonance (SPR). We have explored two SPR assay formats, with either mAb10F12 or His6-SNAP-25 coupled to the biosensor chip. When BoNT/A was incubated with SNAP-25 in solution and the reaction products were captured on a mAb-coated chip, a sensitivity of 5 fM (0.1LD50/ml serum) was obtained. However, this configuration required prior immunoprecipitation of BoNT/A. A sensitivity of 0.5 fM in 10% serum (0.1 LD50/ml serum) was attained when SNAP-25 was coupled directly to the chip, followed by sequential injection of BoNT/A samples and mAb10F12 into the flow system to achieve on-chip cleavage and detection, respectively. This latter format detected BoNT/A endoprotease activity in 50-100 µl serum samples from all patients (11/11) with type A botulism within 5h. No false positives occurred in sera from healthy subjects or patients with other neurological diseases. The automated chip-based procedure has excellent specificity and sensitivity, with significant advantages over the mouse bioassay in terms of rapidity, required sample volume and animal ethics. Copyright © 2014 Elsevier B.V. All rights reserved.
Kumar, Raekha; Lorenc, Ava; Robinson, Nicola; Blair, Mitch
2011-09-01
Traditional and complementary healthcare approaches (TCA) are widely used for children, often because of perceived safety. Honey is a traditional remedy for upper respiratory tract symptoms in infants. Health officials currently advise limiting honey use because of the risk of botulism. This paper discusses honey as a traditional healthcare approach for children in a multi-ethnic community, and parents' and primary healthcare practitioners' (PHPs) perceptions of its safety. As part of a larger study exploring beliefs about TCA, this paper focuses on perceived safety and use of honey, using data extracted for detailed analysis. Eleven parent focus groups (n= 92) and 30 interviews with PHPs were conducted. Qualitative data analysis used the Framework approach. London Boroughs of Brent and Harrow TCA, particularly home remedies, dietary and religious approaches were popular for children. Honey was a particularly common TCA, reportedly used by 27 (29%) parents for their children. Honey was believed to be traditional, acceptable, accessible, natural and safe. It was most commonly used for respiratory tract symptoms and administered with hot water and lemon juice. PHPs were more concerned about the safety of TCA than parents. Almost half (40%) of PHPs mentioned the use of honey for children, few perceived it as a 'treatment' or were concerned about botulism. Others were aware of the risks and some reported challenges in communicating risk to parents. TCA are commonly used for children, honey in particular for respiratory tract symptoms. Parents and some PHPs appear unaware of the risk of botulism from honey use in infants. Healthcare practitioners should ask routinely about the use of honey and other TCA, and consider different parental belief systems in ethnically diverse populations. Further research is required on the use and efficacy of honey for infants, to raise awareness of its benefits and risks. © 2010 Blackwell Publishing Ltd.
The epizootiology of type C botulism in fish-eating birds at Salton Sea, California
Nol, P.
2002-01-01
During 1996, type C avian botulism killed over 15,000 fish-eating birds at the Salton Sea in southern California. Amont those affected were nearly 10,000 western white pelicans (Pelecanus erythrorhynchos) and over 1,200 endangered California brown pelicans (Pelecanus occidentalis californicus). Since 1996, smaller epizootics have occurred every year. Type C botulism is not typically associated with fish-eating birds. In the case of the Salton Sea, Mozambique tilapia (Oreochromis mossambicus) are the suspected source of type C toxin, although the mechanism by which the fish acquire the toxin is still unknown. The goals of this study were to: 1) Determine presence/absence of active Clostridium botulinum type C and type C botulinum toxin in tilapia in the Salton Sea. 2) Use geospatial analyses to evaluate relationships between patterns of mortality in birds and fish and presence/absence of toxin and/or toxin-producing bacteria in sediments and fish. We investigated a method of detecting C. botulinum type C cells in the intestinal contents of Mozambique tilapia. This method involved extraction of predominantly cellular DNA and uses a polymerase chain reaction assay to detect presence of type C toxin gene. We collected sick, dead and healthy fish from various sites throughout the Sea during the summers of 1999 to 2001 in order to test them for the presence of active C. botulinum type C by PCR and for the presence of type C toxin by ELISA and mouse test. The results demonstrate that the tilapia population in the Salton Sea harbors C. botulinum type C cells within their gastrointestinal tract and the prevalence of this organism varies from year to year. The total number of fish with toxin-producing bacteria was significantly greater in 2000 than in 2001. No difference in the numbers of positives was detected between sick and dead fish compared to live fish, and there were no differences noted with regard to location of fish collection. The prevalence of active type C toxin in tilapia was low and the majority of samples positive for toxin by ELISA were negative on mouse test. Further investigation is currently underway. From 1999-2001, routine surveillance was conducted July through November to detect morbidity and mortality in pelicans. Location of retrieval and total number of birds collected were documented. In all three years, the majority of botulism-affected pelicans were retrieved from the vicinities of the river deltas although the Whitewater River had the fewest birds of the three. It has yet to be determined what roles the tilapia and pelican populations play in influencing these patterns.
Emerging Infections and Bioterrorism
2001-09-01
bioterrorism. Some examples of unusual outbreaks that could have been mistaken for bioterrorism are given below: Event/ Disease Location Year Legionnaires ...Geminiviruses) 1 237 Table 2. Viral Hemorrhagic Fevers Family and/or genus Disease ( s ) Arenaviridae Lassa fever, Bolivian HF (Machupo virus), Argentine HF (Junin...bioterrorist agents: these are the organisms or toxins that cause the diseases anthrax, botulism, brucellosis, plague, Q fever, smallpox, staphylococcal
Evaluation of a quali embryo model for the detection of botulism toxin type A activity
USDA-ARS?s Scientific Manuscript database
The Japanese quail embryo (Coturnix japonica) was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving ...
Bibliography of references to avian botulism: Update
Wilson, Sonoma S.; Locke, Louis N.
1982-01-01
This bibliography, first compiled in 1970 (Allen and Wilson 1977) and published in 1977 in response to many requests for information on avian botulism, has been updated to include the literature published through 1980.In general, only articles dealing primarily with the avian disease are included, as opposed to those concerned with the various aspects of the biology of Clostridium botulinum, either type C or E. A few exceptions, such as Bengtson's report of the first isolation and description of the type C organism, are included for their historical interest. Progress reports and other administrative documents not available for distribution on request are excluded, as are most textbook accounts, which are generally summaries of work published elsewhere.This bibliography was a cooperative effort by the National Wildlife Health Laboratory, U.S. Fish and Wildlife Service, and the U.S. National Park Service. The National Park Service provided partial funding for the work through Contract No. 89100-0491.Although the authors attempted to list every important reference, they make no claim to complete coverage of the published literature. The authors will be grateful to users of the bibliography who call attention to errors or omissions.Wayne I. Jensen (Retired)Milton Friend, Director, National Wildlife Health Laboratory
Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.
Kelch, W J; Kerr, L A; Pringle, J K; Rohrbach, B W; Whitlock, R H
2000-09-01
Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.
[Neuromuscular diseases were always difficult to diagnose].
Claus, D
2013-06-01
The Deutsche Zeitschrift fuer Nervenheilkunde (German Journal for Neurology) was founded as a specifically neurological journal at the end of the nineteenth century and soon became a European platform for scientific discussion of neurological topics. Papers also came from the USA, Scandinavia and Russia. The difficulties of the diagnosis and definition of clinical entities are illustrated in cases of botulism, myotonic dystrophy and myasthenia gravis.
DoD Resource Augmentation for Civilian Consequence Management (DRACCM) Tool
2015-07-01
staffing availabilities for the nine regions. Finally, we added options to view IDAC data that had included school closings, vaccinations , antivirals...there is enough critical medical resource at that hospital for a given day. An hospital icon coded yellow means that at least one critical medical...tularemia, Q fever , SEB, anthrax, plague (with contagion), VEE, botulism, brucellosis, glanders, smallpox (with contagion), influenza, cesium, sarin, VX
Jain, Swati; Ponmariappan, S.; Kumar, Om
2011-01-01
Background & objectives: Botulinum neurotoxins (A-G) are among most poisonous substances in the world, produced by obligate anaerobic bacteria Clostridum botulinum. Among the seven serotypes A, B, E and F are of human importance. In India, the prevalence of C. botulinum as well as botulism outbreaks have been reported. Due to its extreme toxicity it has been classified in the Category A of biological warfare agent. So far, there is no commercial detection system available in India to detect botulism. The present study aims to develop an immuno detection system for botulinum neurotoxin serotype B using synthetic gene approach. Methods: The truncated fragment of the botulinum neurotoxin type B from amino acid 1-450 was synthesized using PCR overlap primers; the constructed gene was cloned in the pQE30UA vector and transformed to Escherichia coli SG 13009. The recombinant protein expression was optimized using various concentration of isopropylthiogalactoside (IPTG) induction, further the expression was confirmed by Western blot analysis using anti-His antibody. Recombinant protein was purified under denatured condition using Ni-NTA affinity chromatography. Antibody was generated against the recombinant protein using alum adjuvant in BALB/c mice and tested for cross reactivity with other serotypes of C. botulinum as well as closely related clostridia. An ELISA test was developed for the detection of botulinum neurotoxin and the minimum detection limit was also estimated. Results: The recombinant protein was expressed at maximum yield at 4.3 h of post-induction with 0.5 mM IPTG concentration. The recombinant protein was purified using Ni-NTA affinity chromatography up to the homogeneity level. The polyclonal antibodies were raised in mice with a titre of 1:2048000. The developed antibody was highly specific with a sensitivity of detecting approximately 15 ng/ml of recombinant protein and not showing any cross-reactivity with other serotypes. Interpretation & conclusions: There is no commercial immunodetection system available in India to detect botulism. The developed detection system is highly specific. It will be useful for growing food industry to detect botulinum neurotoxin in food samples as well as in clinical samples. PMID:21808132
Isolation and Functional Characterization of the Novel Clostridium botulinum Neurotoxin A8 Subtype
Kull, Skadi; Schulz, K. Melanie; Strotmeier, Jasmin Weisemann née; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P. Wojtek; Nitsche, Andreas; Kalb, Suzanne R.; Dorner, Martin B.; Barr, John R.; Rummel, Andreas; Dorner, Brigitte G.
2015-01-01
Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might pave the way for the development of novel therapeutics and tailor-made antitoxins. PMID:25658638
Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.
Kull, Skadi; Schulz, K Melanie; Weisemann, Jasmin; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P Wojtek; Nitsche, Andreas; Kalb, Suzanne R; Dorner, Martin B; Barr, John R; Rummel, Andreas; Dorner, Brigitte G
2015-01-01
Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might pave the way for the development of novel therapeutics and tailor-made antitoxins.
Nonhunting mortality in sandhill cranes
Windingstad, R.M.
1988-01-01
Records of 170 sandhill cranes (Grus canadensis) necropsied at the National Wildlife Health Research Center, Wisconsin, from 1976 through 1985 were reviewed as representative samples to determine causes of nonhunting mortality in the mid-continent and Rocky Mountain populations of sandhill cranes. Avian cholera, avian botulism, and ingestion of mycotoxins were leading causes of nonhunting mortality. Hailstorms, lightning, lead poisoning, predation, avian tuberculosis, and collisions with power lines also killed cranes.
Contagious Weakness in an Elderly Couple with Neurologic Emergencies
2011-02-01
affected, causing asphyxiation without ventilator support. Additional findings can include dry mouth , Figure 1. Home canned and processed goods in...specifically “nausea and vomiting, dysphagia, diplopia, dry mouth , and dilated and fixed pupils,” and to administer the antitoxin in consultation with...the intensive care unit ( ICU ) for observation. At that point, we were certain of botulism, given the symptoms in both patients. We contacted the
ERIC Educational Resources Information Center
Funk, Fanchon F.; Bolin, Sheila A.
2002-01-01
In 1999, investigators from Florida's Regal Swan Project researched the care of captive swans in hotels, resorts, educational settings, and municipalities. This led to a vaccine to mitigate swan deaths from botulism and a book with standards and guidelines for swan keepers worldwide. Research was shared through a science and reading curriculum…
Bibliography of Technical Publications and Papers, October 1979 - September 1980
1980-11-01
technological procedures affecting quality of radappertized chicken rolls. Institute of Food Technolo- gists, New Orleans, LA, 9-11 June 1980. 93...temperature survey of ginger beef pot roast production at a Central Food Preparation Facility. J. Food Prot., 43(4): 292-294 (1980). 180. REESE, E. T...low-dose irradiated chicken skins. Interagency Botulism Research Coordinating Coummittee, Milford, CT, 8-9 October 1980. 207. CALLO, B. Protoplast
Modified, Packaged Tortillas Have Long Shelf Life
NASA Technical Reports Server (NTRS)
Bourland, Charles; Glaus-Late, Kimberly
1995-01-01
Tortillas made from modified recipe and sealed in low-pressure nitrogen in foil pouches in effort to increase their shelf life at room temperature. Preliminary tests show that shelf life of these tortillas at least five months; in contrast, commercial tortillas last only few days. Part of water in recipe replaced with glycerin. Particularly necessary to avoid Clostridium botulinum, which grows in anaerobic environments and produces deadly toxin that causes botulism.
Development of Targeted Therapeutic Agents for Botulism
2001-02-01
peptides previously prepared by Schmidt & Bostian (1997) [where changes were made to a C-terminal 17-mer (187-203) of SNAP-25], attention was focussed here...arrest of intoxication with inhibitors (being prepared 8 successfully by Dr. J. Schmidt at USAMRIID; Schmidt et al., 1998) whilst replenshing the toxic...purified on the immobilised immunogen. Urografin (Schering Healthcare, G.D.R.), digitonin (Novabiochem, U.K.), radio -immunoassay (RIA) kit for human growth
Research and Preparation of an Equine Heptavalent Botulinal Antitoxin
1989-02-01
Equine Heptavalent Botulinal Antitoxin". Hyperimmune plasma was obtained by plasmapheresis of two Army horses : a thoroughbred, First Flight, and a black...4x1. II. Materials and Methods A. Immunization of Horses For the purpose of producing equine heptavalent botulInum antitoxin, two horses were...Minnesota these horses were fed specially formulated high protein grain pellets and also a daily ration of hay. Routine health care maintainance, including
USDA-ARS?s Scientific Manuscript database
Comparison of quail (Coturnix japonica) and chicken (Gallus domesticus) embryos for the detection of BoNT/A activity was conducted using equal dosages of toxin/g of embryo (quail at 7 g and chickens at 48 g). Quail embryos were injected at 0, 0.5 to 50 ng and chicken embryos at 0, 3.4 to 342 ng and...
Type C botulism in dairy cattle from feed contaminated with a dead cat
Galey, F.D.; Terra, R.; Walker, R.; Adaska, J.; Etchebarne, M.A.; Puschener, B.; Whitlock, R.H.; Rocke, T.E.; Willoughby, D.; Tor, E.
2000-01-01
Four hundred twenty-seven of 441 adult Holstein dairy cattle from a 1,200-cow dairy died over a 1-week period during early spring 1998. Affected animals were from 4 late lactation pens, one of which included the bull string. Signs included weakness, recumbency, watery diarrhea, and death. Eighty animals from the 4 pens were dead approximately 8 hours after the first ill cows were noted. Affected cows would collapse on stimulation and extend all 4 limbs with moderate rigidity. Several lacked lingual tonus and had abdominal breathing patterns. The animals had been fed a load of total mixed ration that included a rotten bale of oat hay containing a dead cat. No common toxicants were identified, and pathologic examination revealed no consistent lesions. Testing of tissue from the cat carcass found in the feed sample using mouse protection bioassay identified the presence of type C botulinum toxin. Samples of feed, tissue from affected animals, cat tissue from feed, milk, and serum were also tested using an enzyme-linked immunosorbent assay (ELISA) specific for type C botulinum. Two samples of rumen contents were tested and found to be positive for botulism by ELISA, and 1 of 3 liver samples had a weak positive finding. No botulinum toxin was found in milk or sera using the ELISA.
Botulism in the ICU: Nursing care plan.
Zariquiey-Esteva, G; Galeote-Cózar, D; Santa-Candela, P; Castanera-Duro, A
Botulism is a rare disease in Europe, caused by the bacterium Clostridium botulinum, notifiable, non-transmissible person-to-person and potentially fatal (between 5 and 10%) if not treated quickly. The favourable opinion of the Clinical Research Ethics Committee was obtained. We present the nursing care plan of a 49-year-old man with a diagnosis of bacterial intoxication caused by Clostridium botulinum, secondary to ingestion of beans in poor condition, who was admitted to the ICU for a total of 35 days. Holistic nursing evaluation during the first 24hours, with prioritisation of the systems that were deteriorating fastest: neurological and respiratory. Nine diagnoses were prioritised according to the NANDA taxonomy: Risk for allergy response, Ineffective breathing pattern, impaired oral mucous membrane, Impaired physical mobility, Risk for disuse syndrome, Risk for dysfunctional gastrointestinal motility, Impaired urinary elimination, Risk for acute confusion and Risk for caregiver role strain. The nursing care plan, standardised and organised with the NANDA taxonomy and prioritised with the outcome-present state-test (OPT) model, guaranteed the best care based on evidence, as the NOC scores improvement demonstrated. It was impossible to compare the nursing intervention with other case reports. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.
Newell, C R; Ma, Li; Doyle, Michael
2012-06-01
A series of botulism challenge studies were performed to determine the possibility of production of botulinum toxin in mussels (Mytilus edulis) held under a commercial high-oxygen (60 to 65% O(2)), modified atmosphere packaging (MAP) condition. Spore mixtures of six strains of nonproteolytic Clostridium botulinum were introduced into mussel MAP packages receiving different packaging buffers with or without the addition of lactic acid bacteria. Dye studies and package flipping trials were conducted to ensure internalization of spores by packed mussels. Inoculated mussel packages were stored at normal (4°C) and abusive (12°C) temperatures for 21 and 13 days, respectively, which were beyond the packaged mussels' intended shelf life. Microbiological and chemical analyses were conducted at predetermined intervals (a total of five sampling times at each temperature), including total aerobic plate counts, C. botulinum counts, lactic acid bacterial counts, package headspace gas composition, pH of packaging buffer and mussel meat, and botulinum toxin assays of packaging buffer and mussel meat. Results revealed that C. botulinum inoculated in fresh mussels packed under MAP packaging did not produce toxin, even at an abusive storage temperature and when held beyond their shelf life. No evidence was found that packaging buffers or gas composition influenced the lack of botulinum toxin production in packed mussels.
Tracking sources of Clostridium botulinum type E contamination in seal meat.
Leclair, Daniel; Farber, Jeffrey M; Pagotto, Franco; Suppa, Sandy; Doidge, Bill; Austin, John W
2017-01-01
Botulism in Nunavik, Quebec is associated with the consumption of aged marine mammal meat and fat. The objective was to identify meat handling practices presenting a risk of contamination of seal meat with C. botulinum. Potential sources of contamination were assessed through interviews with igunaq producers from five communities of Nunavik. These sources were verified by detection and isolation of C. botulinum from igunaq prepared in the field from seal carcasses. Interviews indicated practices presenting a risk for contamination included: placing meat or fat on coastal rocks, using seawater for rinsing, and ageing meat in inverted seal skin pouches. Although the presence of C. botulinum type E spores was detected in only two of 32 (6.3%) meat or fat samples collected during the butchering process, two of four igunaq preparations from these samples contained type E botulinum toxin. Analysis of C. botulinum type E isolates recovered from these preparations indicated that shoreline soil may be a source of contamination. Seal meat and fat may be contaminated with C. botulinum type E during the butchering process. Measures can be adopted to reduce the risks of contamination in the field and possibly decrease the incidence of type E botulism in Nunavik.
Evaluation of coproexamination as a diagnostic test for avian botulism
Jensen, Wayne I.
1981-01-01
Fecal extracts and blood sera from 113 ducks showing clinical signs of botulism were examined for Clostridium botulinum type C toxin by means of the mouse toxicity test to evaluate coproexamination as a diagnostic procedure, as compared with demonstration of toxin in serum. When death of test mice unprotected with type specific antitoxin (while protected controls survived) was the criterion, 78.8% of the sera and 5.3% of the fecal extracts were positive. When characteristic signs of intoxication in the unprotected mice was included as evidence of toxin in the specimens, these percentages increased to 86.7 and 6.2, respectively.Fecal specimens were collected hourly for the first 6 h after peroral dosing of eight mallards (Anas platyrhynchos) with 1.0 LD50, of type C toxin and at 24, 48, and 72 h from birds surviving that long. From 2 to 4 toxin-positive specimens were passed by all eight ducks during the first 6 h, five specimens were positive at 24 h, and three were positive at 48 h. Only three specimens were collected at 72 h, all of which were negative. These findings suggest that attempts to detect toxin in the feces of wild ducks might have been more successful had the birds been captured earlier in the course of the disease.
The use of Endopep-MS to detect multiple subtypes of botulinum neurotoxins A, B, E, and F
NASA Astrophysics Data System (ADS)
Kalb, Suzanne R.; Smith, Theresa J.; Moura, Hercules; Hill, Karen; Lou, Jianlong; Geren, Isin N.; Garcia-Rodriguez, Consuelo; Marks, James D.; Smith, Leonard A.; Pirkle, James L.; Barr, John R.
2008-12-01
Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. Rapid determination of exposure to BoNT is an important public health goal. Previous work in our laboratory focused on the development of Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT A-G in buffer and BoNT A, B, E, and F in clinical samples. We introduce here the use of Endopep-MS to detect non-commercial subtypes of BoNT A, B, E, and F which have been associated with botulism outbreaks. We have now tested and successfully detected 15 of the 17 known subtypes of BoNT A, B, E, and F by Endopep-MS. Extraction of BoNT A and B from a complex mixture prior to analysis is accomplished by using monoclonal antibodies specific for the catalytically inactive heavy chain of the toxin. These antibodies have high-binding affinities and do not interfere with the catalytic activity of the light chain resulting in a lower limit of detection for BoNT A and B than previously reported. We also report for the first time limits of detection for BoNT A2, A3, B2, and bivalent B using Endopep-MS.
Toxicoinfectious botulism in commercial caponized chickens
Trampel, D.W.; Smith, Susan; Rocke, Tonie E.
2005-01-01
During the summer of 2003, two flocks of commercial broiler chickens experienced unusually high death losses following caponizing at 3 wk of age and again between 8 and 14 wk of age. In September, fifteen 11-wk-old live capons were submitted to the Iowa State University Veterinary Diagnostic Laboratory for assistance. In both flocks, the second episode of elevated mortality was associated with incoordination, flaccid paralysis of leg, wing, and neck muscles, a recumbent body posture characterized by neck extension, and diarrhea. No macroscopic or microscopic lesions were detected in affected chickens. Hearts containing clotted blood and ceca were submitted to the National Wildlife Health Center in Madison, WI. Type C botulinum toxin was identified in heart blood and ceca by mouse bioassay tests. Enzyme-linked immunosorbent assay tests on heart blood samples were also positive for type C botulinum toxin. Clostridium botulinum was isolated from the ceca and genes encoding type C botulinum toxin were detected in cecal contents by a polymerase chain reaction test. Chickens are less susceptible to botulism as they age, and this disease has not previously been documented in broilers as old as 14 wk of age. Wound contamination by spores of C. botulinum may have contributed to the unusually high death losses following caponizing.
Lee, Soomin; Lee, Heeyoung; Kim, Sejeong; Lee, Jeeyeon; Ha, Jimyeong; Choi, Yukyung; Oh, Hyemin; Choi, Kyoung-Hee; Yoon, Yohan
2018-03-13
Nitrite plays a major role in inhibiting the growth of foodborne pathogens, including Clostridium botulinum that causes botulism, a life-threatening disease. Nitrite serves as a color-fixing agent in processed meat products. However, N-nitroso compounds can be produced from nitrite. They are considered as carcinogens. Thus, consumers desire processed meat products that contain lower concentrations (below conventional concentrations of products) of nitrite or no nitrite at all, although the portion of nitrite intake by processed meat consumption in total nitrite intake is very low. However, lower nitrite levels might expose consumers to risk of botulism poisoning due to C. botulinum or illness caused by other foodborne pathogens. Hence, lower nitrite concentrations in combination with other factors such as low pH, high NaCl level, and others have been recommended to decrease the risk of food poisoning. In addition, natural compounds that can inhibit bacterial growth and function as color-fixing agents have been developed to replace nitrite in processed meat products. However, their antibotulinal effects have not been fully clarified. Therefore, to have processed meat products with lower nitrite concentrations, low pH, high NaCl concentration, and others should also be applied together. Before using natural compounds as replacement of nitrite, their antibotulinal activities should be examined.
Causes of mortality in common loons
Franson, J. Christian; Cliplef, David J.
1992-01-01
Summarized are necropsy results from 222 carcasses of Common Loons (Gavia immer) submitted to the National Wildlife Health Research Center from 1976 through 1991. The carcasses were from 18 states, and 10 or more birds each were from Minnesota, Florida, Virginia, Michigan, Wisconsin, Maine, and North Carolina. Seventy-three (33%) carcasses were emaciated, and in some of these birds emaciation was thought to be related to exposure to mercury. OVer 40% of these emaciated birds were from Florida. Trauma, including blunt trauma of unknown origin, outboard motor propeller wounds, and shooting caused the deaths of 49 (22%) loons, 30 of which were from Minnesota. Diseases, primarily avian botulism type E and aspergillosis, account for 39 (18%) moralities and lead poisoning for 14 (6%), 11 of which had fishing sinkers in their stomachs. Most of the avian botulism type E cases occurred during two outbreaks on Lake Michigan. Seven of the 14 lead-poisoned birds were from Minnesota. Nine (4%) birds died of miscellaneous causes and 9 (4%) of drowning, primarily from entanglement in nets. No diagnosis could be reached for 29 (13%) carcasses. Sample bias precludes interpretation of these data to represent actual proportional causes of mortality in the loon population. However, the sample size is sufficient to clearly identify major causes of mortality.
Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.
1999-01-01
A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.
Influence of disease on population model of mid-continent mallards
Samuel, Michael D.
1992-01-01
On numerous occasions, waterfowl deaths caused by disease were highly visible to wildlife managers and to the general public. Thousands of birds died during duck plague, avian botulism and avian cholera outbreaks. Undoubtedly, some disease occurred in waterfowl populations throughout their evolution; however, knowledge of disease epizootiology primarily developed during the past 40-50 years (Wobeser 1981) for diseases that cause massive die-offs (e.g., avian cholera, avian botulism and duck plague). Other diseases, such as avian tuberculosis, aspergillosis, parasite infection and lead poisoning, also occur at chronic levels, but the data remain meager on many of these less spectacular causes of mortality and sublethal forms of disease. However, because chronic losses occur throughout the year, their cumulative effect, as well as the large die-offs, are a potential threat to waterfowl populations (Bellrose 1976, Wobeser 1981). Previous studies (Anderson 1975) demonstrated that 50 percent of the annual mortality in mallard (Anas platyrhynchos) populations is from nonhunting causes. In addition to disease, these causes include predation, accidental deaths, inclement weather and other factors (Stout and Cornwell 1976), which can be confounded by disease. Determination of mortality rates from diseases has been difficult because many biases and inconsistencies are associated with the available data. Assessment of disease prevalence and magnitude of losses is complicated by the spatial and temporal variability of many diseases, the logistic difficulty of studying highly mobile waterfowl populations, and the potentially confounding influences of predation and scavenging on detecting disease-related mortality;. Unless losses are so extensive that they direct attention to a particular area, mortality from disease is easily overlooked (see Zwank et al. 1985). Even when die-offs are evident, mortality from disease may be underestimated because sick waterfowl become debilitated, seek seclusion in dense cover and are removed by efficient predators or scavengers prior to human detection. Our objective was to evaluate the possible effects of three of the most common diseases (friend 1985), avian cholera, avian botulism and lead poisoning, on the population dynamics of mid-continental mallards. We used data from disease outbreaks to develop preliminary estimates of mortality rates and their temporal pattern. A computer model was used to integrate these mortality estimate with other mallard life history characteristics, evaluate the potential effects of these diseases on mallard demographics and assess the need for better information on the effects of disease on mallards.
Beuhler, Michael C; Wittler, Mary A; Ford, Marsha; Dulaney, Anna R
2011-08-01
Many public health entities employ computer-based syndromic surveillance to monitor for aberrations including possible exposures to weapons of mass destruction (WMD). Often, this is done by screening signs and symptoms reported for cases against syndromic definitions. Poison centers (PCs) may offer significant contributions to public health surveillance because of their detailed clinical effect data field coding and real-time data entry. Because improper clinical effect coding may impede syndromic surveillance, it is important to assess this accuracy for PCs. An AAPCC-certified regional PC assessed the accuracy of clinical effect coding by specialists in poison information (SPIs) listening to audio recordings of standard cases. Eighteen different standardized cases were used, consisting of six cyanide, six botulism, and six control cases. Cases were scripted to simulate clinically relevant telephone conversations and converted to audio recordings. Ten SPIs were randomly selected from the center's staff to listen to and code case information from the recorded cases. Kappa scores and the percentage of correctly coding a present clinical effect were calculated for individual clinical effects summed over all test cases along with corresponding 95% confidence intervals. The rate of the case coding by the SPIs triggering the PC's automated botulism and cyanide alerts was also determined. The kappa scores and the percentage of correctly coding a present clinical effect varied depending on the specific clinical effect, with greater accuracy observed for the clinical effects of vomiting and agitation/irritability, and poor accuracy observed for the clinical effects of visual defect and anion gap increase. Lack of correct coding resulted in only 60 and 86% of the cases that met the botulism and cyanide surveillance definitions, respectively, triggering the corresponding alert. There was no difference observed in the percentage of coding a present clinical effect between certified (9.0 years experience) and non-certified (2.4 years experience) specialists. There were no cases of coding errors that resulted in the triggering of a false positive alert. The success of syndromic surveillance depends on accurate coding of signs and symptoms. Although PCs generally contribute high-quality data to public health surveillance, it is important to recognize this potential weak link in surveillance methods.
2008-09-03
shock were biocompatible in vivo, retained potent antibody responses, and were well tolerated by rhesus macaques. Vaccinated primates were completely...results indicate that the vaccines were biocompatible by i.d. administration and physical separation. Seroconversion also occurred after the primary...the vaccinated animals, suggesting that the potency of this vaccine was maintained. Cellular immu- nity , not addressed in our study, may also be
Military Role in Countering Terrorist Use of Weapons of Mass Destruction
1999-04-01
chemical and biological mobile point detection. “The M21 Remote Sensing Chemical Agent Alarm (RSCAAL) is an automatic scanning, passive infrared sensor...The M21 detects nerve and blister agent clouds based on changes in the background infrared spectra caused by the presence of the agent vapor.”15...required if greater than 3 years since last vaccine. VEE Yes Multiple vaccines required. VHF No Botulism Yes SEB No Ricin No Mycotoxin s No Source
1989-11-07
dialyzed against the appropriate medium prior to dilution into the bath. The buccal ganglion in Aplysia contain two large, identified cholinergic neurons...transmitters. Micro-injection of nanomolar final concentrations of BoNT A (Fig. 2A) or B (Fig. 2B) into pre-synaptic cholinergic neurons in the buccal ...already been made to use rat pituitary cells together with patch pipette techniques in this study; this system has facilitated intracellular
Computer-Assisted Communication Device for Botulinum-Intoxicated Patients
2008-01-01
development of small molecule therapeutics for botulinum neurotoxin and on the development of nerve agent pretreatments and therapies . He has published...Souayah, N., Karim, H., Kamin, S.S., McArdle, J. and Marcus, S. (2006) ‘Severe botulism after focal injection of botulinum toxin’, Neurology , Vol...67, pp.1855–1856. Tacket, C.O., Shandera, W.X., Mann, J.M., Hargrett, N.T. and Blake, P.A. (1984) ‘ Equine antitoxin use and other factors that
2015-11-28
preliminary feasibility studies, neat samples of centrifu- gation-clarified milk, green bean juice , or non-alcoholic apple cider were added to ESN...2008). International outbreak of severe botulism with pro- longed toxemia caused by commercial carrot juice . Clin. Infect. Dis. 47, 1245–1251. Simpson...derived from induced plu - ripotent stem cells develop mature phenotypes typical of en- dogenous spinal motoneurons. J. Neurosci. 35, 1291–1306. Van
BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS UPON THE BODY
Dickson, Ernest C.; Shevky, Richard
1923-01-01
A survey of the results of these experiments shows, we believe conclusively, that in botulinus intoxication in cats, dogs, and rabbits there is a specific effect upon the portions of the autonomic nervous system which Gaskell (14) described as the bulbosacral and prosomatic outflows of connector fibers respectively, which results in a blocking of the nerve impulses of these nerves. The experimental as well as the clinical evidence indicates that there is no damage to the nerves of the thoracicolumbar outflow. The exact location of the damage has not been ascertained nor has the mechanism by which the nerve impulse is blocked been determined. The experiments show, however, that the lesions in these portions of the nervous system are not of central distribution but are peripheral, and that the block cannot be due to an organic break in the conduction apparatus but must be due to some derangement which is relatively unstable. If it were otherwise it would not be possible to induce a physiological response even by massive stimulation, nor could the response be subsequently repeated by stimuli which lie within the limits of normal intensity. The application of the results of these experiments to the clinical manifestations of botulism will be discussed in a later report after the effect of the toxin upon the skeletal motor nerves has been described. PMID:19868755
Stanker, Larry H.; Scotcher, Miles C.; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert
2013-01-01
Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A – H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s) for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested. PMID:24253240
Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G
2008-01-01
Background Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. Methods As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. Results The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. Conclusion Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product. PMID:18768085
Activity of botulinum neurotoxin type D (strain 1873) in human neurons
Pellett, Sabine; Tepp, William H.; Scherf, Jacob M.; Pier, Christina L.; Johnson, Eric A.
2015-01-01
Botulinum Neurotoxin type D (BoNT/D) causes periodic outbreaks of botulism in cattle and horses, but is rarely associated with human botulism. Previous studies have shown that humans responded poorly to peripheral injection of up to 10 U of BoNT/D. Isolated human pyramidalis muscle preparations were resistant to BoNT/D, whereas isolated human intercostal muscle preparations responded to BoNT/D similarly as to other BoNT serotypes. In vitro data indicate that BoNT/D does not cleave human VAMP1 efficiently, and differential expression of the VAMP 1 and 2 isoforms may be responsible for the above observations. Here we examined sensitivity of cultured human neurons derived from human induced pluripotent stem cells to BoNT/D. Our data indicate that BoNT/D can enter and cleave VAMP 2 in human neurons, but at significantly lower efficiency than other BoNT serotypes. In addition, BoNT/D had a short duration of action in the cultured neurons, similar to that of BoNT/E. In vivo analyses indicated a slower time to death in mice, as well as a later onset and shorter duration of action than BoNT/A1. Finally, examination of BoNT/D activity in various rodent and human cell models resulted in dramatic differences in sensitivity, indicating a unique cell entry mechanism of BoNT/D. PMID:25937339
Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea
2017-07-20
Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.
Yoneyama, Tohru; Miyata, Keita; Chikai, Tomoyuki; Mikami, Akifumi; Suzuki, Tomonori; Hasegawa, Kimiko; Ikeda, Toshihiko; Watanabe, Toshihiro; Ohyama, Tohru; Niwa, Koichi
2008-12-01
Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.
Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea
2017-01-01
Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay. PMID:28726719
Stanker, Larry H; Scotcher, Miles C; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert
2013-11-18
Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD's) for individual antibodies ranging from 10 to 48 × 10-11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested.
Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris.
Baghban, Roghayyeh; Gargari, Seyed Latif Mousavi; Rajabibazl, Masoumeh; Nazarian, Shahram; Bakherad, Hamid
2016-01-01
Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property. © 2014 International Union of Biochemistry and Molecular Biology, Inc.
Burnett, James C.; Nuss, Jonathan E.; Wanner, Laura M.; Peyser, Brian D.; Du, Hao T.; Gomba, Glenn Y.; Kota, Krishna P.; Panchal, Rekha G.; Gussio, Rick; Kane, Christopher D.; Tessarollo, Lino
2015-01-01
Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling. Motor neurons derived from human embryonic stem (hES) cells were treated with a panel of SFK inhibitors and intoxicated with BoNT serotypes A, B, or E (which are responsible for >95 % of human botulism cases). Subsequently, it was found that bosutinib, dasatinib, KX2-391, PP1, PP2, Src inhibitor-1, and SU6656 significantly antagonized all three of the serotypes. Furthermore, the data indicated that the treatment of hES-derived motor neurons with multiple SFK inhibitors increased the antagonistic effect synergistically. Mechanistically, the small molecules appear to inhibit BoNTs by targeting host pathways necessary for intoxication and not by directly inhibiting the toxins’ proteolytic activity. Importantly, the identified inhibitors are all well-studied with some in clinical trials while others are FDA-approved drugs. Overall, this study emphasizes the importance of targeting host neuronal pathways, rather than the toxin’s enzymatic components, to antagonize multiple BoNT serotypes in motor neurons. PMID:25782580
Immunotherapy for Infectious Diseases: Past, Present, and Future.
Manohar, Akshay; Ahuja, Jasmine; Crane, John K
2015-01-01
Passive immunotherapy for established infections, as opposed to active immunization to prevent disease, remains a tiny niche in the world of antimicrobial therapies. Many of the passive immunotherapies currently available are directed against bacterial toxins, such as botulism, or are intended for agents of bioterrorism such as anthrax, which fortunately has remained rare. The emergence of Ebola virus and multi-drug resistant pathogens, however, may breathe new life into the immunotherapy field as researchers seek non-antibiotic interventions for infectious diseases.
Mechanism of Action of Botulinum Neurotoxin and Overview of Medical Countermeasures for Intoxication
2008-01-01
D.F., Kane , C.T., Comille, F., and Hackley, Jr., B.E. 1999a. Evaluation of phosphoramidon and three synthetic phosphonates for inhibition of botulinum...of botulism. Clin. Toxicol. II: 19-25. Chertow, D.S., Tan, E.T., Maslanka, S., Schulte, J., Bresnitz, E.A., Weisman, RS., Bernstein, J., Marcus , S.M...manner in which the toxin of Clostridiumbotulinum act upon the body . II. The effect upon the voluntary nervous system. J. Exp. Med.38:327-346. Dolly, J.O
1985-11-19
10.6). Unbound toxoid was removed by washing three times with phosphate-buffered saline (pH 7.4) containing 0.05% Triton X-100 (Eastman Organic...MD) in phosphate-buffered saline was added. After a 90 min incubation period at 37*C, the excess conjugate was removed by washing each well three times...3. Cardella, M. A. 1964. Botulinum toxoids, p. 113-129. In K . H. Lewis and K . Cassel, Jr., (ed.), Botulism. U. S. Department of Health, Education
2003-05-01
medical supply blocks. Two available botulism antitoxins—the Centers for Disease Control and Prevention (CDC) trivalent equine antitoxin for serotypes...4th Ed. Fort Detrick, MD. U.S. Army Medical Research Institute of Infectious Diseases ; 2001: 9-12. 3. Sidell, FR, Franz, David R. Overview: Defense...Diagnosis and Treatment of Diseases of Tactical Importance to U.S. Central Command. Aberdeen Proving Ground, MD: U.S. Army Center for Health Promotion and
Evaluation of a Botulinum Toxoid, Type B, for the Prevention of Shaker Foal Syndrome,
1981-11-06
available at this time, To be published in The Proceeding of the 27ta Annual Meeting of the American Association of Equine Practitioners, Nov 28-Dec 2...1981. 19. KEY WORDS (Continu, on reveres aide If necaeewy and Identify by block number) :.~ Toxoid Toxicoinfection Horse BouimPassive Transfer...SFS) is a highly fatal taxicoinfectious form of botulism occurring most often in horses 2 to 8 weeks of age. Clinically SFS is an acute neuromuscular
Kenow, Kevin P.; Ge, Zhongfu; Fara, Luke J.; Houdek, Steven C.; Lubinski, Brian R.
2016-01-01
Avian botulism type E is responsible for extensive waterbird mortality on the Great Lakes, yet the actual site of toxin exposure remains unclear. Beached carcasses are often used to describe the spatial aspects of botulism mortality outbreaks, but lack specificity of offshore toxin source locations. We detail methodology for developing a neural network model used for predicting waterbird carcass motions in response to wind, wave, and current forcing, in lieu of a complex analytical relationship. This empirically trained model uses current velocity, wind velocity, significant wave height, and wave peak period in Lake Michigan simulated by the Great Lakes Coastal Forecasting System. A detailed procedure is further developed to use the model for back-tracing waterbird carcasses found on beaches in various parts of Lake Michigan, which was validated using drift data for radiomarked common loon (Gavia immer) carcasses deployed at a variety of locations in northern Lake Michigan during September and October of 2013. The back-tracing model was further used on 22 non-radiomarked common loon carcasses found along the shoreline of northern Lake Michigan in October and November of 2012. The model-estimated origins of those cases pointed to some common source locations offshore that coincide with concentrations of common loons observed during aerial surveys. The neural network source tracking model provides a promising approach for identifying locations of botulinum neurotoxin type E intoxication and, in turn, contributes to developing an understanding of the dynamics of toxin production and possible trophic transfer pathways.
Molecular epidemiology of infant botulism in California and elsewhere, 1976-2010.
Dabritz, Haydee A; Hill, Karen K; Barash, Jason R; Ticknor, Lawrence O; Helma, Charles H; Dover, Nir; Payne, Jessica R; Arnon, Stephen S
2014-12-01
Infant botulism (IB), first identified in California in 1976, results from Clostridium botulinum spores that germinate, multiply, and produce botulinum neurotoxin (BoNT) in the immature intestine. From 1976 to 2010 we created an archive of 1090 BoNT-producing isolates consisting of 1012 IB patient (10 outpatient, 985 hospitalized, 17 sudden death), 25 food, 18 dust/soils, and 35 other strains. The mouse neutralization assay determined isolate toxin type (56% BoNT/A, 32% BoNT/B). Amplified fragment-length polymorphism (AFLP) analysis of the isolates was combined with epidemiologic information. The AFLP dendrogram, the largest to date, contained 154 clades; 52% of isolates clustered in just 2 clades, 1 BoNT/A (n=418) and 1 BoNT/B (n=145). These clades constituted an endemic C. botulinum population that produced the entire clinical spectrum of IB. Isolates from the patient's home environment (dust/soil, honey) usually located to the same AFLP clade as the patient's isolate, thereby identifying the likely source of infective spores. C. botulinum A(B) strains were identified in California for the first time. Combining molecular methods and epidemiological data created an effective tool that yielded novel insights into the genetic diversity of C. botulinum and the clinical spectrum, occurrence, and distribution of IB in California. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Polar poisons: did Botulism doom the Franklin expedition?
Horowitz, B Zane
2003-01-01
In 1845 the Franklin expedition left London with 2 ships and 134 men on board in an attempt to find the route through the Northwest Passage. The ships were built with state-of-the-art technology for their day, but provisioned with supplies from the lowest bidder. After taking on fresh provisions in the Whalefish Islands, off the coast of Greenland, the entire crew was never heard from again. Graves found on remote Beechey Island indicate that three able-bodied seamen died during the first winter. A note written on a ship's log, later found in a cairn, indicate that the expedition's leader, Sir John Franklin, died during the second winter entrapped on the ice, by which time 24 men had also perished. The remaining crew failed in their attempt to walk out of the Arctic by an overland route. In 1981 Owen Beattie, from the University of Alberta, exhumed the remains of the sailors from the three graves on Beechey Island. Elevated lead levels were found in all three sailors. While lead poisoning has been a leading theory of the cause of the crew's deaths, blamed on the crudely tinned provisions the ships carried with them from England, chronic lead exposure may only have weakened the crew, not necessarily killed them. One of three exhumed sailors also had in his intestine the spores of an unspecified Clostridium species. The theory put forth by this article is that Botulism, type E, which is endemic in the Arctic, may have been responsible for their deaths.
Ihekwaba, Adaoha E C; Mura, Ivan; Walshaw, John; Peck, Michael W; Barker, Gary C
2016-11-01
Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics.
Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay.
Williamson, Charles H D; Vazquez, Adam J; Hill, Karen; Smith, Theresa J; Nottingham, Roxanne; Stone, Nathan E; Sobek, Colin J; Cocking, Jill H; Fernández, Rafael A; Caballero, Patricia A; Leiser, Owen P; Keim, Paul; Sahl, Jason W
2017-09-15
Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Coding region sequences unique to each of the four species/subgroups were identified by in silico analyses of thousands of genome assemblies, and PCR primers were designed to amplify each marker. The resulting multiplex PCR assay correctly assigned 41 tested isolates to the appropriate species or subgroup. A separate PCR assay to determine the presence of the ntnh gene (a gene associated with the botulinum neurotoxin gene cluster) was developed and validated. The ntnh gene PCR assay provides information about the presence or absence of the botulinum neurotoxin gene cluster and the type of gene cluster present ( ha positive [ ha + ] or orfX + ). The increased availability of whole-genome sequence data and comparative genomic tools enabled the design of these assays, which provide valuable information for characterizing BoNT-producing clostridia. The PCR assays are rapid, inexpensive tests that can be applied to a variety of sample types to assign isolates to species/subgroups and to detect clostridia with botulinum neurotoxin gene ( bont ) clusters. IMPORTANCE Diverse clostridia produce the botulinum neurotoxin, one of the most potent known neurotoxins. In this study, a multiplex PCR assay was developed to differentiate clostridia that are most commonly isolated in connection with human botulism cases: C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Since BoNT-producing and nontoxigenic isolates can be found in each species, a PCR assay to determine the presence of the ntnh gene, which is a universally present component of bont gene clusters, and to provide information about the type ( ha + or orfX + ) of bont gene cluster present in a sample was also developed. The PCR assays provide simple, rapid, and inexpensive tools for screening uncharacterized isolates from clinical or environmental samples. The information provided by these assays can inform epidemiological studies, aid with identifying mixtures of isolates and unknown isolates in culture collections, and confirm the presence of bacteria of interest. Copyright © 2017 Williamson et al.
2003-04-01
botulism, immune globulin , plague, and meningncocu.s). Among the 11,441 Culf War veterans, a total of 4601 Gulf veterans (40.2%)) self-reported (S-R...administered (typhoid, borulinum toxoid, immune globulin , plague, and meningococus). This variable was coded as the sum of the number of vaccines...parametric Wilcoxon signecl- ranks test was used to assess whether the prc\\lalencc in S-R yes group was the same as the prevalcncc in the S-R n o
Efficacy of 3,4-Diaminopyridine as a Therapy for Type C Botulism
1986-12-09
0 of type A botulinum neurotoxin. The difference in the effectiveness of 3,-LAPaanttpD n ouiu toxins may be due to variations in the mechanism of...effectiveness of 3,4-DAP against t4a A and C botulinum toxins may be due to variations in the mechanism of action of these neurotoxins at the molecular...contained 2.0 X 107 LDsdml. For the production of type C toxin , the Stockholm strain of Clostridium botulinum type C was grown in a medium containing 2.0
[Botulism: structure and function of botulinum toxin and its clinical application].
Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko
2012-08-01
Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.
Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders.
Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia
2015-09-23
Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a "glamour" drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.
Infant botulism in Andalusia (Southern Spain).
López-Laso, Eduardo; Roncero-Sánchez-Cano, Inés; Arce-Portillo, Elena; Ley-Martos, Myriam; Aguirre-Rodríguez, Javier; García-Ron, Adrián; Mora-Navarro, David; Méndez-García, Mario; Camino-León, Rafael
2014-05-01
Infant botulism (IB) is caused by the intestinal colonization by Clostridium botulinum in the first year of life and its subsequent production of neurotoxins. Traditionally, IB has been associated to honey consumption. IB cases tend to cluster in geographic regions. In Europe, IB is a rare disorder. From 1976 through 2006, 65 cases were identified in 13 European countries. In Spain, in the last 15 years, most of the cases have been reported in one region, Andalusia (Southern Spain). A specific treatment for IB type A and type B (BabyBIG) is available outside of the United States since 2005. and aims: We performed a retrospective review of IB cases detected in Andalusia since 1997 and compare them with the cases of IB reported in Europe. We identified 11 confirmed cases of IB in Andalusia since 1997, and 14 cases in Spain. Nine out of 11 cases were detected since 2007; none of these infants had been exposed to honey consumption. One case in 1997 and another in 2000 were associated to honey. Two cases were treated with BabyBIG in 2007. In the period 2006-2012 the cases of IB reported in Europe were 54. We identified a considerable increase in the incidence of IB since 2006. A tendency to a reduction in the number of cases of IB linked to honey consumption has also been identified. An increase in the exposure to these bacteria from the environment could be presumed. Clinicians should maintain a high index of suspicion for this treatable disorder. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.
Cheng, Luisa W; Henderson, Thomas D
2011-07-01
Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.
Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders
Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia
2015-01-01
Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377
Walshaw, John; Peck, Michael W.; Barker, Gary C.
2016-01-01
Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161
Webb, Robert P.; Smith, Theresa J.; Smith, Leonard A.; Wright, Patrick M.; Guernieri, Rebecca L.; Brown, Jennifer L.; Skerry, Janet C.
2017-01-01
There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering have resulted in subsequent vaccine efforts being primarily focused on the production of highly purified recombinant protein antigens representing one or more domains of the botulinum neurotoxin. Recombinant subunit vaccines based on the carboxy one-third of the toxin (Hc) developed in our lab against serotypes A-F have been shown to be safe and effective. However, in response to the identification of an ever increasing number of BoNT subtypes with significant amino acid heterogeneity, we have developed catalytically inactive BoNT holoproteins (ciBoNT HPs) in an attempt to elicit greater protective immunity to address these toxin variants. Here we report the production of ciBoNT/B1 HP, ciBoNT/C1 HP, ciBoNT/E1 HP and ciBoNT/F1 HP and compare the immunological and protective abilities of ciBoNT HPs and BoNT/A Hc, BoNT/B Hc, BoNT/C Hc, BoNT/E Hc and BoNT/F Hc vaccines when challenged with homologous and heterologous toxins. Our results suggest the ciBoNT HP vaccines exhibit superior potency after single vaccinations but multiple vaccinations with BoNT/Hc antigens resulted in increased survival rates at the toxin challenge levels used. PMID:28869522
Wang, Dongxia; Krilich, Joan; Baudys, Jakub; Barr, John R.; Kalb, Suzanne R.
2015-01-01
It is essential to have a simple, quick and sensitive method for the detection and quantification of botulinum neurotoxins, the most toxic substances and the causative agents of botulism. Type C botulinum neurotoxin (BoNT/C) represents one of the seven members of distinctive BoNT serotypes (A to G) that cause botulism in animals and avians. Here we report the development of optimized peptide substrates for improving the detection of BoNT/C and /CD mosaic toxins using an Endopep-MS assay, a mass spectrometry-based method that is able to rapidly and sensitively detect and differentiate all types of BoNTs by extracting the toxin with specific antibodies and detecting the unique cleavage products of peptide substrates. Based on the sequence of a short SNAP-25 peptide, we conducted optimization through a comprehensive process including length determination, terminal modification, single and multiple amino acid residue substitution, and incorporation of unnatural amino acid residues. Our data demonstrate that an optimal peptide provides a more than 200-fold improvement over the substrate currently used in the Endopep-MS assay for the detection of BoNT/C1 and /CD mosaic. Using the new substrate in a four-hour cleavage reaction, the limit of detection for the BoNT/C1 complex spiked in buffer, serum and milk samples was determined to be 0.5, 0.5 and 1 mouseLD50/mL, respectively, representing a similar or higher sensitivity than that obtained by traditional mouse bioassay. PMID:25913863
Electrochemical Aptamer Scaffold Biosensors for Detection of Botulism and Ricin Proteins.
Daniel, Jessica; Fetter, Lisa; Jett, Susan; Rowland, Teisha J; Bonham, Andrew J
2017-01-01
Electrochemical DNA (E-DNA) biosensors enable the detection and quantification of a variety of molecular targets, including oligonucleotides, small molecules, heavy metals, antibodies, and proteins. Here we describe the design, electrode preparation and sensor attachment, and voltammetry conditions needed to generate and perform measurements using E-DNA biosensors against two protein targets, the biological toxins ricin and botulinum neurotoxin. This method can be applied to generate E-DNA biosensors for the detection of many other protein targets, with potential advantages over other systems including sensitive detection limits typically in the nanomolar range, real-time monitoring, and reusable biosensors.
Cost of irradiating bacon and the associated energy savings. Technical report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brynjolfsson, A.
1979-03-01
This paper is about costs and energy savings obtained by irradiating bacon. Sterilized by irradiation (25 kGy), bacon without added nitrite does not contain nitrosamines and does not constitute botulism hazard. If bacon is irradiation sterilized while refrigerated, the cost of irradiation is about $0.08/lb; if irradiation-sterilized while frozen, the costs of irradiation and freezing would be about $0.03/lb. Substerilizing irradiation doses of 7.5 to 15 kGy would give about 80 days extension of bacon stored and distributed refrigerated. The irradiation costs, in this case, would be about $0.07/lb.
[Ocular disturbances in neuromuscular disorders].
Pénisson-Besnier, I; Lamirel, C
2008-11-01
Compared with other skeletal muscles, extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain neuromuscular disorders. When the oculomotor signs are predominant, their temporal progression allows the clinician to make the distinction between a muscular disease (mitochondrial disorder, oculopharyngeal muscular dystrophy...) and a disorder of the neuromuscular junction (myasthenia gravis, botulism...). In other instances, such as myotonic dystrophy or facioscapulohumeral dystrophy, the ocular signs are not in the forefront but must be recognized by the ophthalmologist as hallmarks of a muscular disorder. In all cases, the collaboration between the neurologist and the ophthalmologist is fruitful.
Ruet, Alexis; Durand, Marie Christine; Denys, Pierre; Lofaso, Frederic; Genet, François; Schnitzler, Alexis
2015-06-01
To characterize electromyographic abnormalities according to symptoms (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin injection. Retrospective, single-center study comparing single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis oculi (OO) muscles. Hospital. Four groups of adults treated for spasticity or neurologic bladder hyperactivity (N=55): control group (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness: n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20), and botulism group (from intensive care unit of the same hospital: n=3). Not applicable. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers were compared between groups. SFEMG was abnormal for 17.6% of control patients and 75% of patients in the pseudobotulism group. There were no differences between the control and fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers of the EDC muscle were significantly higher in the pseudobotulism group than in the fatigue and control groups. There were no differences between groups for the OO muscle. The SFEMG results in the botulism group were qualitatively similar to those of the pseudobotulism group. SFEMG of the EDC muscle confirmed diffusion of the toxin into muscles distant from the injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin type A were found away from the injection site in patients with fatigue but no motor weakness. Such fatigue may be related to other mechanisms. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Development and Validation of a New Reliable Method for the Diagnosis of Avian Botulism.
Le Maréchal, Caroline; Rouxel, Sandra; Ballan, Valentine; Houard, Emmanuelle; Poezevara, Typhaine; Bayon-Auboyer, Marie-Hélène; Souillard, Rozenn; Morvan, Hervé; Baudouard, Marie-Agnès; Woudstra, Cédric; Mazuet, Christelle; Le Bouquin, Sophie; Fach, Patrick; Popoff, Michel; Chemaly, Marianne
2017-01-01
Liver is a reliable matrix for laboratory confirmation of avian botulism using real-time PCR. Here, we developed, optimized, and validated the analytical steps preceding PCR to maximize the detection of Clostridium botulinum group III in avian liver. These pre-PCR steps included enrichment incubation of the whole liver (maximum 25 g) at 37°C for at least 24 h in an anaerobic chamber and DNA extraction using an enzymatic digestion step followed by a DNA purification step. Conditions of sample storage before analysis appear to have a strong effect on the detection of group III C. botulinum strains and our results recommend storage at temperatures below -18°C. Short-term storage at 5°C is possible for up to 24 h, but a decrease in sensitivity was observed at 48 h of storage at this temperature. Analysis of whole livers (maximum 25 g) is required and pooling samples before enrichment culturing must be avoided. Pooling is however possible before or after DNA extraction under certain conditions. Whole livers should be 10-fold diluted in enrichment medium and homogenized using a Pulsifier® blender (Microgen, Surrey, UK) instead of a conventional paddle blender. Spiked liver samples showed a limit of detection of 5 spores/g liver for types C and D and 250 spores/g for type E. Using the method developed here, the analysis of 268 samples from 73 suspected outbreaks showed 100% specificity and 95.35% sensitivity compared with other PCR-based methods considered as reference. The mosaic type C/D was the most common neurotoxin type found in examined samples, which included both wild and domestic birds.
Development and Validation of a New Reliable Method for the Diagnosis of Avian Botulism
Le Maréchal, Caroline; Rouxel, Sandra; Ballan, Valentine; Houard, Emmanuelle; Poezevara, Typhaine; Bayon-Auboyer, Marie-Hélène; Souillard, Rozenn; Morvan, Hervé; Baudouard, Marie-Agnès; Woudstra, Cédric; Mazuet, Christelle; Le Bouquin, Sophie; Fach, Patrick; Popoff, Michel; Chemaly, Marianne
2017-01-01
Liver is a reliable matrix for laboratory confirmation of avian botulism using real-time PCR. Here, we developed, optimized, and validated the analytical steps preceding PCR to maximize the detection of Clostridium botulinum group III in avian liver. These pre-PCR steps included enrichment incubation of the whole liver (maximum 25 g) at 37°C for at least 24 h in an anaerobic chamber and DNA extraction using an enzymatic digestion step followed by a DNA purification step. Conditions of sample storage before analysis appear to have a strong effect on the detection of group III C. botulinum strains and our results recommend storage at temperatures below -18°C. Short-term storage at 5°C is possible for up to 24 h, but a decrease in sensitivity was observed at 48 h of storage at this temperature. Analysis of whole livers (maximum 25 g) is required and pooling samples before enrichment culturing must be avoided. Pooling is however possible before or after DNA extraction under certain conditions. Whole livers should be 10-fold diluted in enrichment medium and homogenized using a Pulsifier® blender (Microgen, Surrey, UK) instead of a conventional paddle blender. Spiked liver samples showed a limit of detection of 5 spores/g liver for types C and D and 250 spores/g for type E. Using the method developed here, the analysis of 268 samples from 73 suspected outbreaks showed 100% specificity and 95.35% sensitivity compared with other PCR-based methods considered as reference. The mosaic type C/D was the most common neurotoxin type found in examined samples, which included both wild and domestic birds. PMID:28076405
Steinman, A; Chaffer, M; Elad, D; Shpigel, N Y
2006-08-01
The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle prompted us to determine vaccine efficacy and reasons for vaccine failure. Analysis of clinical signs, feeding practice, vaccination history, and epidemic curves enabled us to define a study population in two outbreaks, where high doses of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the affected animal groups. Attack rates among unvaccinated 6- to 24-month-old heifers were 96% (55/57) and 85% (53/62). The attack rates in vaccinated parity 1, 2, and >or=3 cows were 40.4% (21/52), 14.3% (4/28), and 5.6% (3/54), respectively. Vaccine efficacies for these cow groups were 52.5%, 83.2%, and 93.4%, respectively. In younger, unvaccinated 2- to 6-month-old calves, presumably protected by maternal antibodies, the attack rate was 24% (17/71). These differences correlated with significant differences in levels of specific anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA). The ELISA performance for predicting protection was analyzed by receiver operating characteristic analysis and was found to be highly significant, with an area under the curve of 0.941 (standard error, 0.034; 95% confidence interval, 0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33 were affected in these exposed groups. At this cutoff level, the specificity of the ELISA was 100%, sensitivity was 67%, and accuracy was 92%. We concluded that botulinum toxoids can confer adequate protection against natural exposure to lethal doses of BoNT/D; however, the vaccination protocols should be optimized. Our in-house ELISA system will enable us to optimize vaccination protocols in the animal population.
Leysath, Clinton E.; Ofori, Kwasi; Baldwin, Karen; Feng, Xiaochuan; Bedenice, Daniela; Webb, Robert P.; Wright, Patrick M.; Smith, Leonard A.; Tzipori, Saul; Shoemaker, Charles B.
2012-01-01
Antitoxins are needed that can be produced economically with improved safety and shelf life compared to conventional antisera-based therapeutics. Here we report a practical strategy for development of simple antitoxin therapeutics with substantial advantages over currently available treatments. The therapeutic strategy employs a single recombinant ‘targeting agent’ that binds a toxin at two unique sites and a ‘clearing Ab’ that binds two epitopes present on each targeting agent. Co-administration of the targeting agent and the clearing Ab results in decoration of the toxin with up to four Abs to promote accelerated clearance. The therapeutic strategy was applied to two Botulinum neurotoxin (BoNT) serotypes and protected mice from lethality in two different intoxication models with an efficacy equivalent to conventional antitoxin serum. Targeting agents were a single recombinant protein consisting of a heterodimer of two camelid anti-BoNT heavy-chain-only Ab VH (VHH) binding domains and two E-tag epitopes. The clearing mAb was an anti-E-tag mAb. By comparing the in vivo efficacy of treatments that employed neutralizing vs. non-neutralizing agents or the presence vs. absence of clearing Ab permitted unprecedented insight into the roles of toxin neutralization and clearance in antitoxin efficacy. Surprisingly, when a post-intoxication treatment model was used, a toxin-neutralizing heterodimer agent fully protected mice from intoxication even in the absence of clearing Ab. Thus a single, easy-to-produce recombinant protein was as efficacious as polyclonal antiserum in a clinically-relevant mouse model of botulism. This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit. PMID:22238680
Mukherjee, Jean; Tremblay, Jacqueline M; Leysath, Clinton E; Ofori, Kwasi; Baldwin, Karen; Feng, Xiaochuan; Bedenice, Daniela; Webb, Robert P; Wright, Patrick M; Smith, Leonard A; Tzipori, Saul; Shoemaker, Charles B
2012-01-01
Antitoxins are needed that can be produced economically with improved safety and shelf life compared to conventional antisera-based therapeutics. Here we report a practical strategy for development of simple antitoxin therapeutics with substantial advantages over currently available treatments. The therapeutic strategy employs a single recombinant 'targeting agent' that binds a toxin at two unique sites and a 'clearing Ab' that binds two epitopes present on each targeting agent. Co-administration of the targeting agent and the clearing Ab results in decoration of the toxin with up to four Abs to promote accelerated clearance. The therapeutic strategy was applied to two Botulinum neurotoxin (BoNT) serotypes and protected mice from lethality in two different intoxication models with an efficacy equivalent to conventional antitoxin serum. Targeting agents were a single recombinant protein consisting of a heterodimer of two camelid anti-BoNT heavy-chain-only Ab V(H) (VHH) binding domains and two E-tag epitopes. The clearing mAb was an anti-E-tag mAb. By comparing the in vivo efficacy of treatments that employed neutralizing vs. non-neutralizing agents or the presence vs. absence of clearing Ab permitted unprecedented insight into the roles of toxin neutralization and clearance in antitoxin efficacy. Surprisingly, when a post-intoxication treatment model was used, a toxin-neutralizing heterodimer agent fully protected mice from intoxication even in the absence of clearing Ab. Thus a single, easy-to-produce recombinant protein was as efficacious as polyclonal antiserum in a clinically-relevant mouse model of botulism. This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit.
2012-07-03
doses. (Mark all that apply) 0 Typhoid 0 Meningococcal 0 Yellow Fever 0 Other. list: 0 No 0 Don’t know Anti-malarial medications 0 ChiOfoquine...Smallpox Ueaves a seer on the arm I 0 Anthrax 0 Botulism 0 Typhoid 0 Meningococcal 0 Other, list: 0 Don’t know 0 None 5. Otd you take any of the...did you develop them anytime during tt.is deployment? No Yes During Yes Now 0 0 0 Chronic cough 0 0 0 Runny nose 0 0 0 Fever 0 0 0 Weakness 0 0
Historical overview of key issues in food safety.
Foster, E. M.
1997-01-01
Foodborne transmission of pathogenic and toxigenic microorganisms has been a recognized hazard for decades. Even half a century ago we knew about the dangers of botulism from underprocessed canned foods; staphylococcal poisoning from unrefrigerated cream-filled pastries, sliced ham, meat, and poultry salads; and salmonellosis from infected animal products. Despite new protective measures, changes in preservation techniques and failure to follow recognized procedures have created new dangers. Moreover, we now recognize new organisms that can cause foodborne illness--Listeria monocytogenes, Escherichia coli O157:H7, Campylobacter jejuni, Vibrio parahaemolyticus, Yersinia enterocolitica, and others. Controlling these organisms will require widespread education and possibly new regulatory initiatives. PMID:9366600
2007-03-16
A p o p f b a © K 1 c s r h a d t f f r i 0 d Vaccine 25 (2007) 4273–4282 Protection with recombinant Clostridium botulinum C1 and D binding domain...reserved. r-bindin s r t r w i t l s eywords: Botulinum neurotoxin subtypes; Recombinant vaccine; Recepto . Introduction Botulism is the collective term...amedd.army.mil (L.A. Smith). e c t B i T c s 264-410X/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. oi:10.1016/j.vaccine
Sacroiliac Joint Interventions.
Soto Quijano, David A; Otero Loperena, Eduardo
2018-02-01
Sacroiliac joint (SIJ) pain is an important cause of lower back problems. Multiple SIJ injection techniques have been proposed over the years to help in the diagnosis and treatment of this condition. However, the SIJ innervation is complex and variable, and truly intra-articular injections are sometimes difficult to obtain. Different sacroiliac joint injections have shown to provide pain relief in patients suffering this ailment. Various techniques for intraarticular injections, sacral branch blocks and radiofrequency ablation, both fluoroscopy guided and ultrasound guided are discussed in this paper. Less common techniques like prolotherapy, platelet rich plasma injections and botulism toxin injections are also discussed. Copyright © 2017 Elsevier Inc. All rights reserved.
Confronting bioterrorism: physicians on the front line.
Varkey, Prathibha; Poland, Gregory A; Cockerill, Franklin R; Smith, Thomas F; Hagen, Philip T
2002-07-01
The events surrounding September 11, 2001, and its aftermath have compelled the public health and medical community to face the hitherto unfamiliar reality of bioterrorism. Physicians and public health personnel are frontline soldiers in this new form of warfare. This article provides a general overview of the pathophysiology, clinical presentation, diagnosis, and management of patients infected with the 6 highest priority agents that could potentially be used in bioterrorism. The diseases discussed include anthrax, smallpox, tularemia, plague, botulism, and viral hemorrhagic fevers. Despite the unpredictable nature of bioterrorism, disaster preparedness and knowledge of essential diagnostic and epidemiological principles can contribute substantially toward combating this new threat.
Pellett, Sabine; Tepp, William H.; Bradshaw, Marite; Kalb, Suzanne R.; Dykes, Janet K.; Lin, Guangyun; Nawrocki, Erin M.; Pier, Christina L.; Barr, John R.; Maslanka, Susan E.
2016-01-01
ABSTRACT Botulinum neurotoxins (BoNTs), produced by neurotoxigenic clostridial species, are the cause of the severe disease botulism in humans and animals. Early research on BoNTs has led to their classification into seven serotypes (serotypes A to G) based upon the selective neutralization of their toxicity in mice by homologous antibodies. Recently, a report of a potential eighth serotype of BoNT, designated “type H,” has been controversial. This novel BoNT was produced together with BoNT/B2 in a dual-toxin-producing Clostridium botulinum strain. The data used to designate this novel toxin as a new serotype were derived from culture supernatant containing both BoNT/B2 and novel toxin and from sequence information, although data from two independent laboratories indicated neutralization by antibodies raised against BoNT/A1, and classification as BoNT/FA was proposed. The sequence data indicate a chimeric structure consisting of a BoNT/A1 receptor binding domain, a BoNT/F5 light-chain domain, and a novel translocation domain most closely related to BoNT/F1. Here, we describe characterization of this toxin purified from the native strain in which expression of the second BoNT (BoNT/B) has been eliminated. Mass spectrometry analysis indicated that the toxin preparation contained only BoNT/FA and confirmed catalytic activity analogous to that of BoNT/F5. The in vivo mouse bioassay indicated a specific activity of this toxin of 3.8 × 107 mouse 50% lethal dose (mLD50) units/mg, whereas activity in cultured human neurons was very high (50% effective concentration [EC50] = 0.02 mLD50/well). Neutralization assays in cells and mice both indicated full neutralization by various antibodies raised against BoNT/A1, although at 16- to 20-fold-lower efficiency than for BoNT/A1. IMPORTANCE Botulinum neurotoxins (BoNTs), produced by anaerobic bacteria, are the cause of the potentially deadly, neuroparalytic disease botulism. BoNTs have been classified into seven serotypes, serotypes A to G, based upon their selective neutralization by homologous antiserum, which is relevant for clinical and diagnostic purposes. Even though supportive care dramatically reduces the death rate of botulism, the only pharmaceutical intervention to reduce symptom severity and recovery time is early administration of antitoxin (antiserum raised against BoNTs). A recent report of a novel BoNT serotype, serotype H, raised concern of a “treatment-resistant” and highly potent toxin. However, the toxin’s chimeric structure and characteristics indicate a chimeric BoNT/FA. Here we describe the first characterization of this novel toxin in purified form. BoNT/FA was neutralized by available antitoxins, supporting classification as BoNT/FA. BoNT/FA required proteolytic activation to achieve full toxicity and had relatively low potency in mice compared to BoNT/A1 but surprisingly high activity in cultured neurons. PMID:27303710
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lijinsky, W.
At low doses dietary nitrite has no obvious deleterious effect, even when ingested for long periods, and nitrites have been used for a long time as flavoring and coloring additives to meat and fish and as preservatives in food in which there is a danger of botulism. In recent years there has been increasing concern that one form of activation of nitrite might be related to cancer. That is the property of interaction with amino compounds to form N-nitroso compounds, which are potent chemical carcinogens. Results are reported from studies on the carcinogenic effects of nitrite and amines in rats.more » (CH)« less
NASA Astrophysics Data System (ADS)
Jacobson, Mark Joseph; Johnson, Eric A.
The clostridia have a rich history and contemporary importance in industrial, environmental, and medical microbiology. Due to their ability to form endospores, clostridia are ubiquitous in nature and are found in many environments, especially in soils and the intestinal tract of animals including humans. Many clostridia cause devastating diseases of humans and animals, such as botulism, tetanus, and gas gangrene, through the production of protein toxins. The clostridia produce more protein toxins that are lethal for humans and animals than any other bacterial genus (Johnson, 2005; Van Heyningen, 1950). Other species are important in the formation of solvents and organic acids by anaerobic fermentations or as a source of unique enzymes for biocatalysis (Bradshaw and Johnson, 2010; Hatheway and Johnson, 1998).
Waterfowl botulism--a brief summary
Pearson, G.; Jensen, W.
1994-01-01
If toxin production cannot be controlled by reducing the quantity of suitable media, another step is to prevent the ingestion of the toxic food items. Birds may be chased or lured from areas of toxin source or areas can be made less attractive by rapid and complete drainage, or draw down to a stable shoreline, where wind flooding does not occur. Removal of vertebrate carcasses, especially those of birds dying during the outbreak, reduces the availability of toxic maggots but carcass removal must be carried out frequently and diligently.Prevention of the effects of the toxin can be accomplished in some instances. Some degree of active immunity can be produced by injections of specific toxoi
Botulinum neurotoxins: new questions arising from structural biology.
Kammerer, Richard A; Benoit, Roger M
2014-11-01
Botulinum neurotoxins (BoNTs) are the most toxic substances known and cause botulism in vertebrates. They have also emerged as effective and powerful reagents for cosmetic and medical applications. One important prerequisite for understanding BoNT function in disease, and the further development of the toxins for cosmetic and medical applications, is a detailed knowledge of BoNT interactions with non-toxic neurotoxin-associated proteins and cell surface receptors. Based on the substantial recent progress in obtaining high-resolution crystal structures of key BoNT complexes, we summarize the major advances in understanding BoNT interactions and discuss the resulting potential implications, in particular those relating to BoNT serotype A. Copyright © 2014 Elsevier Ltd. All rights reserved.
Microbiology and foodborne pathogens in honey.
Grabowski, N T; Klein, G
2017-06-13
Honey has been considered a relatively safe foodstuff due to its compositional properties, with infant botulism caused by Clostridium botulinum being the most prominent health risk associated with it. Our review is focused on the honey microflora along the food chain and evaluates the pathogenic potential of those microorganisms found in honey. This product may contain a great variety of bacteria and, particularly, fungi that eventually entered the food chain at an early stage (e.g., via pollen). For many of these microorganisms, opportunistic infections in humans have been recorded (e.g., infections by Staphylococcus spp., Citrobacter spp., Escherichia coli, Hafnia alvei, Aspergillus spp., Fusarium spp., Trichoderma spp., Chaetomium spp.), although direct infections via honey were not registered.
Yalamanchili, Chinni; Manda, Vamshi K; Chittiboyina, Amar G; Guernieri, Rebecca L; Harrell, William A; Webb, Robert P; Smith, Leonard A; Khan, Ikhlas A
2017-02-02
Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest. Fifteen plants were selected from the book 'Diagnosis and treatment of diseases in Ayurveda' by Vaidya Bhagwan Dash and Lalitesh Kashyap, based on their frequency of use in the formulations used for the treatment of six diseases with neuromuscular symptoms similar to botulism. Phytochemicals from these plants were screened using in silico, and in vitro methods. Structures of 570 reported phytochemicals from 14 plants were docked inside six reported BoNT/A light chain crystal structures using ensemble docking module in Maestro (Schrödinger, LLE). From the docking scores and structural diversity, nine compounds including acoric acid 1, three flavonoids, three coumarins derivatives, one kava lactone were selected and screened using an in vitro HPLC-based protease assay. The bioassay results showed that several compounds possess BoNT/A LC inhibition of 50-60% when compared to positive controls NSC 84094 and CB7967495 (80-95%). Further testing of the active compounds identified from Ayurvedic literature and structure-activity studies of acoric acid 1 using more sensitive bioassays is under way. The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Pulsotype Diversity of Clostridium botulinum Strains Containing Serotypes A and/or B Genes
Halpin, Jessica L.; Joseph, Lavin; Dykes, Janet K.; McCroskey, Loretta; Smith, Elise; Toney, Denise; Stroika, Steven; Hise, Kelley; Maslanka, Susan; Lúquez, Carolina
2017-01-01
Clostridium botulinum strains are prevalent in the environment and produce a potent neurotoxin that causes botulism, a rare but serious paralytic disease. In 2010, a national PulseNet database was established to curate C. botulinum pulsotypes and facilitate epidemiological investigations, particularly for serotypes A and B strains frequently associated with botulism cases in the United States. Between 2010 and 2014 we performed pulsed-field gel electrophoresis (PFGE) using a PulseNet protocol, uploaded the resulting PFGE patterns into a national database, and analyzed data according to PulseNet criteria (UPGMA clustering, Dice coefficient, 1.5% position tolerance, and 1.5% optimization). A retrospective data analysis was undertaken on 349 entries comprised of type A and B strains isolated from foodborne and infant cases to determine epidemiological relevance, resolution of the method, and the diversity of the database. Most studies to date on the pulsotype diversity of C. botulinum have encompassed very small sets of isolates; this study, with over 300 isolates, is more comprehensive than any published to date. Epidemiologically linked isolates had indistinguishable patterns, except in four instances and there were no obvious geographic trends noted. Simpson’s Index of Diversity (D) has historically been used to demonstrate species diversity and abundance within a group, and is considered a standard descriptor for PFGE databases. Simpson’s Index was calculated for each restriction endonuclease (SmaI, XhoI), the pattern combination SmaI-XhoI, as well as for each toxin serotype. The D values indicate that both enzymes provided better resolution for serotype B isolates than serotype A. XhoI as the secondary enzyme provided little additional discrimination for C. botulinum. SmaI patterns can be used to exclude unrelated isolates during a foodborne outbreak, but pulsotypes should always be considered concurrently with available epidemiological data. PMID:28692343
Substrate Binding Mode and its Implication on Drug Design for Botulinum Neurotoxin A
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kumaran, D.; Rawat, R; Ahmed, A
2008-01-01
The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins, the causative agents of botulism, block the neurotransmitter release by specifically cleaving one of the three SNARE proteins and induce flaccid paralysis. The Centers for Disease Control and Prevention (CDC) has declared them as Category A biowarfare agents. The most potent among them, botulinum neurotoxin type A (BoNT/A), cleaves its substrate synaptosome-associated protein of 25 kDa (SNAP-25). An efficient drug for botulism can be developed only with the knowledge of interactions between the substrate and enzyme at the active site. Here, we report the crystal structures of the catalytic domain ofmore » BoNT/A with its uncleavable SNAP-25 peptide 197QRATKM202 and its variant 197RRATKM202 to 1.5 A and 1.6 A, respectively. This is the first time the structure of an uncleavable substrate bound to an active botulinum neurotoxin is reported and it has helped in unequivocally defining S1 to S5? sites. These substrate peptides make interactions with the enzyme predominantly by the residues from 160, 200, 250 and 370 loops. Most notably, the amino nitrogen and carbonyl oxygen of P1 residue (Gln197) chelate the zinc ion and replace the nucleophilic water. The P1?-Arg198, occupies the S1? site formed by Arg363, Thr220, Asp370, Thr215, Ile161, Phe163 and Phe194. The S2? subsite is formed by Arg363, Asn368 and Asp370, while S3? subsite is formed by Tyr251, Leu256, Val258, Tyr366, Phe369 and Asn388. P4?-Lys201 makes hydrogen bond with Gln162. P5?-Met202 binds in the hydrophobic pocket formed by the residues from the 250 and 200 loop. Knowledge of interactions between the enzyme and substrate peptide from these complex structures should form the basis for design of potent inhibitors for this neurotoxin.« less
Steinman, A.; Chaffer, M.; Elad, D.; Shpigel, N. Y.
2006-01-01
The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle prompted us to determine vaccine efficacy and reasons for vaccine failure. Analysis of clinical signs, feeding practice, vaccination history, and epidemic curves enabled us to define a study population in two outbreaks, where high doses of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the affected animal groups. Attack rates among unvaccinated 6- to 24-month-old heifers were 96% (55/57) and 85% (53/62). The attack rates in vaccinated parity 1, 2, and ≥3 cows were 40.4% (21/52), 14.3% (4/28), and 5.6% (3/54), respectively. Vaccine efficacies for these cow groups were 52.5%, 83.2%, and 93.4%, respectively. In younger, unvaccinated 2- to 6-month-old calves, presumably protected by maternal antibodies, the attack rate was 24% (17/71). These differences correlated with significant differences in levels of specific anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA). The ELISA performance for predicting protection was analyzed by receiver operating characteristic analysis and was found to be highly significant, with an area under the curve of 0.941 (standard error, 0.034; 95% confidence interval, 0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33 were affected in these exposed groups. At this cutoff level, the specificity of the ELISA was 100%, sensitivity was 67%, and accuracy was 92%. We concluded that botulinum toxoids can confer adequate protection against natural exposure to lethal doses of BoNT/D; however, the vaccination protocols should be optimized. Our in-house ELISA system will enable us to optimize vaccination protocols in the animal population. PMID:16893985
Sanford, Daniel C; Barnewall, Roy E; Vassar, Michelle L; Niemuth, Nancy; Metcalfe, Karen; House, Robert V; Henderson, Ian; Shearer, Jeffry D
2010-09-01
A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD(50)) and to estimate 50% lethal exposure concentrations relative to time (LCt(50)) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD(50) and LCt(50) for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.
Sanford, Daniel C.; Barnewall, Roy E.; Vassar, Michelle L.; Niemuth, Nancy; Metcalfe, Karen; House, Robert V.; Henderson, Ian; Shearer, Jeffry D.
2010-01-01
A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD50) and to estimate 50% lethal exposure concentrations relative to time (LCt50) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD50 and LCt50 for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication. PMID:20660138
Outbreak of type C botulism in birds and mammals in the Emilia Romagna region, northern Italy.
Defilippo, Francesco; Luppi, Andrea; Maioli, Giulia; Marzi, Dario; Fontana, Maria Cristina; Paoli, Federica; Bonilauri, Paolo; Dottori, Michele; Merialdi, Giuseppe
2013-10-01
Over a 7-day period beginning 8 August 2011, a large number of wild birds of several species were found dead or with neurologic clinical signs along the shore of Crostolo stream, in the Emilia Romagna region, Italy. Twenty-eight Mallards (Anas platyrhynchos), two Hooded Crows (Corvus corone cornix), and three coypus (Myocastor coypus) were found moribund on the Crostolo stream bank, collected, and sent to Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Reggio Emilia Section. The cause of mortality was determined to be Clostridium botulinum type C toxin. The toxin was identified by a mouse bioassay for botulinum toxins and confirmed in bird sera and blowfly larvae (Lucilia caesar) collected from the stomachs of birds.
Current gaps in basic science knowledge of botulinum neurotoxin biological actions.
Rossetto, Ornella; Pirazzini, Marco; Montecucco, Cesare
2015-12-01
Botulinum neurotoxins are produced by anaerobic spore-forming bacteria of the genus Clostridium in several dozens of variants that inactivate neurotransmitter release owing to their metalloprotease activity. This results in a persistent paralysis of peripheral nerve terminals known as botulism. They are the most potent toxins known and are classified as one of the six highest-risk threat agents of bioterrorism. Despite their high toxicity, two of them are used as valuable pharmaceutical for the therapy of many neurological and non-neurological disorders. Notwithstanding the many advances in our understanding of the genetics and structure of botulinum neurotoxins, there are still many gaps in knowledge of toxin mechanism of action that will be discussed here. Copyright © 2015 Elsevier Ltd. All rights reserved.
Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.
Guarner, Jeannette; Zaki, Sherif R
2006-01-01
From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Coppock, R.W.; Ross, S.; Reynolds, J.D.
1990-06-01
The death of common loons (Gavia immer) was associated with a small spill of bunker-C oil off the Chicago shoreline of Lake Michigan. Petroleum oil was not found on the feathers or in the lungs of the birds. Botulinus toxins C and E were found in heart blood. Because the carcasses were autolysed, botulism toxins could have been produced postmortem. An average of 97 micrograms PCBs (Aroclor 1254 standard) and 2.2 micrograms dieldrin/g of body fat also were found. Concentrations of heavy metals in one bird were 0.25 microgram of total mercury and 0.5 microgram of lead/g of liver, respectively.more » The loons had abundant body fat suggesting they were not debilitated at the time of death.« less
A rare cause of acute flaccid paralysis: Human coronaviruses
Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir
2015-01-01
Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time. PMID:26557177
A rare cause of acute flaccid paralysis: Human coronaviruses.
Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S Paksu; Haydar, A Tasdemir
2015-01-01
Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.
Oliveira, Ademar Francisco de; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier
2016-01-01
Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. RESUMO Esclerose lateral amiotrófica é uma doença neurodegenerativa progressiva e fatal, caracterizada pela degeneração dos neurônios motores, as células do sistema nervoso central que controlam os movimentos voluntários dos músculos. A salivação excessiva (sialorreia) está presente em cerca de 50% dos casos de esclerose lateral amiotrófica. Dessa forma, surgem medidas terapêuticas alternativas como drogas anticolinérgicas e cirurgia, e recentemente, o uso da toxina botulínica, aplicada em um ponto central das glândulas salivares, muitas vezes guiado por ultrassonografia, demostrou resultados positivos. Objetivou-se revisar a literatura no intuito de demonstrar um método alternativo aos tratamentos de sialorreia em pacientes com esclerose lateral amiotrófica. Em estudos recentes, a eficácia do tratamento com toxina botulínica foi confirmada e, mesmo requerendo novas aplicações, os efeitos colaterais são ínfimos. Ela surge então como alternativa não só ao tratamento de esclerose lateral amiotrófica, mas também para outros pacientes com doenças que apresentem a sialorreia.
Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...
2014-05-22
Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ 70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less
Fernández, Pablo S.; Peck, Michael W.
1999-01-01
Refrigerated processed foods of extended durability such as cook-chill and sous-vide foods rely on a minimal heat treatment at 70 to 95°C and then storage at a refrigeration temperature for safety and preservation. These foods are not sterile and are intended to have an extended shelf life, often up to 42 days. The principal microbiological hazard in foods of this type is growth of and toxin production by nonproteolytic Clostridium botulinum. Lysozyme has been shown to increase the measured heat resistance of nonproteolytic C. botulinum spores. However, the heat treatment guidelines for prevention of risk of botulism in these products have not taken into consideration the effect of lysozyme, which can be present in many foods. In order to assess the botulism hazard, the effect of heat treatments at 70, 75, 80, 85, and 90°C combined with refrigerated storage for up to 90 days on growth from 106 spores of nonproteolytic C. botulinum (types B, E, and F) in an anaerobic meat medium containing 2,400 U of lysozyme per ml (50 μg per ml) was studied. Provided that the storage temperature was no higher than 8°C, the following heat treatments each prevented growth and toxin production during 90 days; 70°C for ≥2,545 min, 75°C for ≥463 min, 80°C for ≥230 min, 85°C for ≥84 min, and 90°C for ≥33.5 min. A factorial experimental design allowed development of a predictive model that described the incubation time required before the first sample showed growth, as a function of heating temperature (70 to 90°C), period of heat treatment (up to 2,545 min), and incubation temperature (5 to 25°C). Predictions from the model provided a valid description of the data used to generate the model and agreed with observations made previously. PMID:10427033
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Yun; Fry, H. Christopher; Skinner, Guy E.
Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 mu g for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Forster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active formsmore » of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U.S. from 2012 to 2015. Each peptide probe contains an enzymatic cleavage site specific to only one serotype. QDs were selected based on the spectral overlap with the quenchers. In the presence of the target BoNT serotype, the peptide probe is cleaved and the quenching of QD photoluminescence (PL) is reduced, giving a signal that is easily detected by a PL spectrophotometer. This sensor performance was evaluated with light chains of BoNT/A and BoNT/B (LcA and LcB), catalytic domains of the respective serotypes. LcA and LcB were detected in 3 h with limits of detection of 0.2 and 2 ng/mL, respectively. The specificity of the sensor was evaluated, and no cross-reactivity from nontarget serotypes was observed with 2 h of incubation. Because each serotype-specific peptide is conjugated to a QD with a unique emission wavelength, multiple biologically active BoNT serotypes could be detected in one PL spectrum. The sensor was also shown to be responsive to BoNT/A and BoNT/B holotoxins. Good performance of this sensor implies its potential application as a rapid screening method for biologically active BoNT/A and BoNT/B in the laboratory and in the field.« less
Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.
Tehran, Domenico Azarnia; Pirazzini, Marco
2018-05-10
Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.
Botulinum neurotoxin homologs in non-Clostridium species.
Mansfield, Michael J; Adams, Jeremy B; Doxey, Andrew C
2015-01-30
Clostridial neurotoxins (CNTs) are the deadliest toxins known and the causative agents of botulism and tetanus. Despite their structural and functional complexity, no CNT homologs are currently known outside Clostridium. Here, we report the first homologs of Clostridium CNTs within the genome of the rice fermentation organism Weissella oryzae SG25. One gene in W. oryzae S25 encodes a protein with a four-domain architecture and HExxH protease motif common to botulinum neurotoxins (BoNTs). An adjacent gene with partial similarity to CNTs is also present, and both genes seem to have been laterally transferred into the W. oryzae genome from an unknown source. Identification of mobile, CNT-related genes outside of Clostridium has implications for our understanding of the evolution of this important toxin family. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Hayashi, Shintaro; Akiyama, Tomonori; Sagane, Yoshimasa; Miyashita, Shin-Ichiro; Watanabe, Toshihiro; Yajima, Shunsuke; Niwa, Koichi
2014-03-01
The botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kDa molecular weight (HA-33). The amino-acid sequence of the C-terminal half of HA-33 of the serotype C strain Yoichi (C-Yoichi) shares only 46% identity with those of the major serotype C strains. Additionally, C-Yoichi HA-33 exhibits a unique sugar-binding specificity. In the present work, C-Yoichi HA-33 was expressed in Escherichia coli and crystallized. Diffraction data were collected at a resolution of 2.2 Å. The crystals belonged to space group R3. The complete detailed protein structure will yield insight into how the unique HA-33 protein recognizes sugar moieties.
Bioterrorism web site resources for infectious disease clinicians and epidemiologists.
Ferguson, Natalie E; Steele, Lynn; Crawford, Carol Y; Huebner, Nathan L; Fonseka, Jamila C; Bonander, Jason C; Kuehnert, Matthew J
2003-06-01
Finding bioterrorism-related information on the World Wide Web can be laborious. We hope to help readers find such information more easily by summarizing essential information in a consistent framework. A panel of 7 Centers for Disease Control and Prevention reviewers identified Web sites and evaluated them for sponsorship, mission, content usefulness, online ease of use, and adherence to commonly accepted quality criteria. Of >100 potential sites identified, 81 were chosen for target content of interest, and 43 were selected for inclusion. The results were classified into general purpose/portal sites; biological agent information; laboratory, infection control, epidemiology, and mental health information; and emergency contact sources, news and updates, event preparedness resources, information for first-responder settings, clinical and public education materials, and research resources. Agents covered included anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fever.