An Outbreak of Botulinum Types A,B, and E Associated With Vacuum-Packaged Salted Fish and Ham

BackgroundBotulinum toxin is a neurotoxin generated during the growth of Clostridium botulinum and can lead to a rare but life-threatening disease with neurologic symptoms. Relatively little is known about the many types of botulinum toxins in China. The clinical symptoms of the different types of botulism toxin–induced illnesses appear after an incubation period and vary greatly by the serotype and degree of exposure to the toxin.Case ReportWe describe 4 patients who consumed vacuum-packaged salted fish and ham and then presented with severe gastrointestinal symptoms, resulting in vomiting and one death. Blood serum and urine samples tested by the botulinum neurotoxin Endopep-MS assay were positive for botulinum toxin types A, B, and E. The patient who consumed the largest amount of fish and ham died after 36 h, and the other patients were treated with botulism antitoxin after being diagnosed with a botulinum toxin–induced illness and recovered after 1 month. These cases illustrate the importance of early diagnosis and early treatment of botulism type E, in particular, because of the risk of respiratory failure and treatment delays, which can result in increased mortality and poorer overall outcomes.Why Should an Emergency Physician Be Aware of This?Our cases illustrate the importance of early diagnosis and especially the treatment of illnesses related to botulism type E because of the risk of respiratory failure and because treatment delays can result in increased mortality and worsened overall outcomes.     

Shot by a Gun … Missed by a Provider

Background

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.

Clostridium botulinum: an increasing complication of heroin misuse.

Wound botulism is a rare infectious disease due to neurotoxin release from the anaerobic, spore-forming bacterium Clostridium botulinum that is becoming an ever more frequent complication of parenteral drug abuse in the Western world. Before the year 2000, no such cases had been reported in the UK and Ireland, but since then the number of proven and suspected cases of wound botulism occurring in parenteral drug users has increased markedly. The diagnosis is often difficult, based on a high degree of clinical suspicion and if not considered in the initial differential diagnosis, then considerable delays in treatment may result. This is the case report of a male heroin user who presented three times to an Emergency Department in the UK before a diagnosis of wound botulism was made and treatment commenced. It is important that emergency clinicians are aware of the possibility of wound botulism in parenteral drug users that present with unusual neurological or respiratory symptomatology.     

引起我国首例婴儿肉毒中毒丁酸梭菌全基因组序列分析

  目的  对我国首次分离自婴儿肉毒中毒病例粪便样品的1株产E型肉毒毒素的丁酸梭菌进行全基因组测序，解析菌株产毒的遗传学特性。  方法  对从婴儿肉毒中毒病例粪便样品中分离的产E型肉毒毒素丁酸梭菌分离株TJ-S提取基因组DNA，利用Pacific Biosciences RSⅡ 平台对菌株进行全基因组测序，并进行序列分析。  结果  TJ-S基因组由一个染色体和一个质粒组成，大小分别为3 949 987 bp和747 151 bp。 GC含量分别为28.8%和28.2%。 染色体上携带产肉毒毒素的bont/e基因，该基因位于典型orfX基因簇内，且在基因簇上游存在3个转座酶编码基因。 遗传进化分析发现，菌株TJ-S在亲缘关系上与引起英国婴儿肉毒中毒的2株产E型肉毒毒素的丁酸梭菌分离株最为接近。  结论  丁酸梭菌携带的产E型肉毒毒素基因位于稳定的orfX基因簇内，可引起人类肉毒中毒。 本报道是我国第一次对产E型肉毒毒素丁酸梭菌进行全基因组学分析。     

肉毒抗毒素现状和发展趋势概述

肉毒毒素是已知毒性最强的生物毒素,其引起的肉毒中毒时有发生,甚至会致死.肉毒抗毒素是目前唯一的肉毒中毒特异性治疗手段,尽早使用肉毒抗毒素对提高肉毒中毒的治疗效果具有重要意义.目前国内外批准上市的肉毒抗毒素基本都是马源性制剂,存在引起过敏反应等不良反应的风险.本文对肉毒抗毒素的国内外现状、生产工艺、质量控制和临床应用等现...     

Food-borne botulism

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.     

Infant botulism: case report and clinical update

Infant botulism occurs in infants between 1 week and 11 months of age and results from the in vivo production of neurotoxin by Clostridium botulinum. The clinical spectrum ranges from asymptomatic carriers, through various degrees of paralysis, to sudden death. The classic clinical presentation is an afebrile child with constipation and generalized weakness manifested by poor head control, poor suck, and weak cry. Symptoms can progress to include cranial nerve palsies, respiratory arrest, and adynamic ileus. Treatment is supportive in an intensive care setting. Antibiotics and antitoxin are not indicated. The morbidity and mortality is less than 3% in hospitalized patients and complete recovery can be expected. The environmental and dietary factors associated with infection are discussed.     

Susceptibility of Clostridium botulinum to thirteen antimicrobial agents.

A total of 224 strains of Clostridium botulinum (including isolates from 14 patients with infant botulism and 4 with wound botulism) and 15 strains of C. sporogenes were tested by agar dilution for susceptibility to tetracycline, metronidazole, erythromycin, penicillin, rifampin, chloramphenicol, clindamycin, cephalothin, cefoxitin, vancomycin, sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. At least 90% of the C. botulinum strains tested (except for nonproteolytic strains of toxin type F with penicillin) were susceptible to all drugs except sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. Minimal inhibitory concentrations for strains from patients with infant and wound botulism were similar to those for other C. botulinum strains.     

Bacterial toxins with intracellular protease activity

The recent determination of their primary sequence has lead to the discovery of the metallo-proteolytic activity of the bacterial toxins responsible for tetanus, botulism and anthrax. The protease domain of these toxins enters into the cytosol where it displays a zinc-dependent endopeptidase activity of remarkable specificity. Tetanus neurotoxin and botulinum neurotoxins type B, D, F and G cleave VAMP, an integral protein of the neurotransmitter containing synaptic vesicles. Botulinum neurotoxins type A and E cleave SNAP-25, while the type C neurotoxin cleaves both SNAP-25 and syntaxin, two proteins located on the cytosolic face of the presynaptic membrane. Such specific proteolysis leads to an impaired function of the neuroexocytosis machinery with blockade of neurotransmitter release and consequent paralysis. The lethal factor of Bacillus anthracis is specific for the MAPkinase-kinases which are cleaved within their amino terminus. In this case, however, such specific biochemical lesion could not be correlated with the pathogenesis of anthrax. The recently determined sequence of the vacuolating cytotoxin of Helicobacter pylori contains within its amino terminal domain elements related to serine-proteases, but such an activity as well as its cytosolic target remains to be detected.     

Mode of action of botulinum neurotoxin: pathological, cellular and molecular aspect]

Several bacteria of the Clostridium genus (C. botulinum) produce 150 kDa di-chainal protein toxins referred as botulinum neurotoxins or BoNTs. They associate with non-toxic companion proteins and form a complex termed botulinum toxin or BoTx. The latter is used in clinic for therapeutic purpose. BoNTs affect cholinergic nerve terminals in periphery where they block acetylcholine release, thereby causing dysautonomia and motorparalysis (i.e. botulism). The cellular action of BoNTs can be depicted according to a three steps model: binding, internalisation and intraneuronal action. The toxins heavy chain mediates binding to specific receptors followed by endocytotic internalisation of BoNT/receptor complex. BoNT receptors may comprise gangliosides and synaptic vesicle-associated proteins as synaptotagmins. Vesicle recycling induces BoNT internalisation. Upon acidification of vesicles, the light chain of the neurotoxin is translocated into the cytosol. Here, this zinc-endopeptidase cleaves one or two among three synaptic proteins (VAMP-synaptobrevin, SNAP25, and syntaxin). As the three protein targets of BoNT play major role in fusion of synaptic vesicles at the release sites, their cleavage is followed by blockage of neurotransmitter exocytosis. The duration of the paralytic effect of the BoNTs is determined by 1) the turnover of their protein target; 2) the time-life of the toxin light chain in the cytosol, and 3) the sprouting of new nerve-endings that are retracted when the poisoned nerve terminal had recovered its full functionality.     

肉毒杆菌食物中毒急诊救治一例

肉毒杆菌食物中毒是由肉毒杆菌释放的肉毒毒素引起严重的神经肌肉中毒症状。该病初期常因临床表现为急性胃肠道中毒症状引起误诊而耽误治疗,严重者导致患者死亡。及早明确诊断和临床对症治疗是成功救治该病的关键。该文总结分析1例肉毒杆菌食物中毒患者的急诊救治过程。经过详细询问该患者的发病史和进食史,进行全面的体格检查、常规检验、影像辅助检查和实验室血浆肉毒毒素检测分析并结合临床症状,该患者确诊为肉毒毒素中毒。在未明确肉毒毒素亚型情况下,对患者大剂量注射A、B型抗肉毒毒素,辅助抗感染和营养恢复神经功能的综合治疗取得较好的治疗效果。患者发病第7日症状好转,救治26 d后康复出院。     

新疆维吾尔自治区乌鲁木齐市一起肉毒中毒事件调查分析

  目的  通过对新疆维吾尔自治区乌鲁木齐市一起肉毒中毒事件进行调查分析和实验室检测,并采取有效措施预防。  方法  通过查阅就诊记录、访谈相关医生并通过入户调查方式进行现场流行病学调查,采集病例粪便、剩余食物等进行肉毒毒素实验室检测及分型鉴定。  结果  确诊病例2例,均被收治入院。 使用A、B型肉毒抗毒素治疗后, 症状明显缓解。 实验室分离到肉毒梭菌,经荧光定量PCR方法检测携带A型毒素基因,确定为A型肉毒梭菌,小鼠实验检测到A型肉毒毒素。  结论  本次事件是一起由家庭自制豆豉引起的肉毒梭菌中毒,由A型肉毒梭菌污染导致,建议加强居民教育,防止食品制作和储存环节污染。     

Botulinum toxin

Botulinum toxin is regarded as the most lethal substance known. It is estimated that the human LD50 for inhalation botulism is 1 to 3 nanograms of toxin/kilogram body mass. Although only three cases of inhalational botulism have been described, an understanding of the pathophysiology of food-borne outbreaks, wound botulism, and infant botulism, and their therapies, enables the medical community to plan treatment in the event of an aerosol release of botulinum toxin. Antitoxin, vaccine, and F(ab')2 immune fragment therapies are discussed as adjuncts to supportive therapy.     

Botulism: a rare complication of injecting drug use

Botulism is a rare, naturally occurring disease that may also be caused by deliberate or accidental exposure to the toxins of Clostridium botulinum. The three types of naturally occurring disease are food-borne, wound and intestinal colonisation botulism, dependent on the route of ingress of the toxins. Food related botulism remains rare in the UK, but wound botulism is increasing, particularly associated with intravenous drug use. It presents with an afebrile, descending, symmetrical, flaccid paralysis of motor and autonomic but not sensory nerves. Respiratory failure can occur rapidly with little prior ventilatory deterioration. Management includes respiratory support, specific antitoxin and surgical debridement and antibiotics for cases of wound botulism. We report a case of wound botulism and discuss the presenting features that should alert the emergency physician to the diagnosis of wound botulism.     

一例婴儿B型肉毒中毒的实验室诊断

目的对2019年2月来自北京儿童医院1例疑似肉毒中毒的婴儿粪便样品进行实验室诊断，判定是否为肉毒毒素中毒。方法按照GB 4789.12 — 2016稀释处理样品，利用动物实验鉴定肉毒毒素、接种增菌培养基观察变化、采用卵黄培养基进行分离纯化，扩增测序16S rRNA基因并进行序列比对，采用荧光定量PCR方法进行毒素基因分型。结果粪便样本稀释后对小鼠进行腹腔注射，小鼠出现呼吸急促、腹式呼吸，并在4～6 h内死亡，呈现肉毒中毒典型症状。 在卵黄培养基平板上分离到典型肉毒梭菌，镜检观察到芽孢形态，测得的16S rRNA基因序列与GenBank中公开的肉毒梭菌16S rRNA基因序列进行比对，相似率>99%，荧光定量PCR检测显示B型毒素基因阳性，判定该婴儿为B型肉毒中毒。结论此次实验按照国家标准和本实验室建立的荧光定量PCR方法进行鉴定，检测结果和诊断方案为我国婴儿B型肉毒中毒诊断提供参考，也为分析肉毒中毒地域性提供证据，为临床鉴定婴儿B型肉毒中毒提供参考案例。     

Botulism,where are we now?

Introduction.?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. Aim.?The aim of this review is to summarize the current knowledge on the microbiology, epidemiology, vaccine research and clinical management of human botulism. Conclusions.?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.     

Type E botulism

There are seven known serotypes of botulism, designated A through G; almost all human cases of botulism are caused by types A, B, and E. Botulism type E is the predominant serotype causing disease associated with native Arctic foods. In the circumpolar regions of the world, the coastal soils are rich in botulism type E, and consumption of fish and marine animals in these areas are the sources of clusters of botulism. Unlike spores of type A and B, botulism type E can withstand freezing down to 3.5°C. Alaskan native fermentation of fish heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum toxin to be elaborated from Clostridium botulinum. The consumption of whale meat, "muktuk" has also been associated with outbreaks of botulism in Alaska and the Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been associated with Norwegian "rakfisk" prepared by a process similar to fermented Alaskan foods. Outbreaks in Egypt with the salted gray mullet "faseikh", in Israel and New York linked to salted uneviscerated whitefish "kapchunka", in Iran from eating "ashbal" an uncooked salmon, and in Japan with "izushi" a traditional fermented fish preserved in rice have occurred. Importation of vacuum-packed whitefish from Alaska and Canada has also been associated with sporadic cases of botulism type E in Europe. In March 2010, the Center for Disease Control and Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under an Investigational New Drug program, as the preferred treatment for food-borne botulism, including type E, which had not been covered by the bivalent antitoxin, the prior approved antitoxin product in the USA.     

Infantile Botulism: Clinical Manifestations,Treatment, and the Role of the Nurse Practitioner

Clostridium botulinum, a toxin most commonly found in soil and honey products, is the main source of infantile botulism. Botulinum toxin is one of the most deadly substances that can attack the neuromuscular system, resulting in a wide range of sequelae. A high index of suspicion is crucial in promptly diagnosing and treating infantile botulism because of the potential for abrupt progression into respiratory failure. This article discusses the epidemiology, pathophysiology, and clinical manifestations of infantile botulism, as well as the valuable role the nurse practitioner plays in preventing this disease within the pediatric population.     

Descending polyneuropathy in an intravenous drug user.

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.     

Type A botulism from commercially canned beef stew.

Two of three persons who ate lunch together became ill with symptoms characteristic of botulism. One died before botulism was suspected and before specimens could be collected for laboratory testing, but a serum specimen from the other patient, who survived, yielded botulinal toxin, type A. The third person remained asymptomatic, but Clostridium botulinum type A was cultured from his stool. The three persons had shared two canned foods: home-canned green beans and commercially canned beef stew. The green beans were initially assumed to be the cause of the outbreak. However, the empty stew can was recovered from the garbage, and washings from the can yielded C botulinum, type A, and its toxin.