Severe Botulism Research Articles

Botulinum toxin and botulism. A clinical case.

Botulism is an acute infectious disease caused by a neutrotoxin produced by the bacterium Clostridium botulinum and characterized by severe bulbar lesions. Botulism is characterized by the complexity of diagnosis and in adverse cases can lead to death. At the moment, in the complex therapy of botulism, the introduction of a mixture of antitoxic serums is mandatory. In addition to specific treatment, pathogenetic therapy is performed for all patients. Specific prophylaxis is carried out with polyanatoxin to a narrow group of people in contact with Clostridium botulinum or their toxins. However, neutralizing anti-botulinum antibodies may be detected in the blood serum of a number of individuals, which have a protective effect when encountering an infection. This article presents a clinical case of severe botulism in an adult patient with simultaneous absence of symptoms of the disease in family members.Botulinum toxin preparations have long been used in aesthetic medicine. It is worth noting that the botulinum toxin molecule has a high molecular weight and can cause an immune response with repeated injections, especially in areas rich in lymph nodes. Forming specific antibodies belong to the IgG class and may have neutralizing properties. In the above clinical case, the patient’s wife, during repeated injections of botulinum toxin, most likely, the formation of neutralizing antibodies occurred, which, in turn, protected the woman from the disease.

Сlinical and epidemiological characteristics of botulism

Clinical and epidemiological characteristics of botulism in the Astrakhan region for the period from 2013 to 2019 are presented. 37 people with a diagnosis of Botulism were under observation. It was found that most often (28 (75.7%) cases) patients associated their disease with the use of canned home-made products. Canned vegetables (cucumbers, tomatoes, vegetable salad, eggplant, cabbage) were consumed by 18 (48.7%) people, mushrooms 10 (27%), dried fish 7 (18.9%), herring-balyk 1 (2.7%) and home-made liver pate-1 (2.7%) patient. The incubation period in the observed patients was on average 2.4 days. It lasted 12 days in 24 (64.9%) patients, 3-5 days in 12 (32.4%) patients, and 6 days in 1 (2.7%) patient. According to the severity of the condition, 17 (45.9%) patients were hospitalized in the intensive care unit. Severe course of the disease was in 17 (45.9%) patients, moderate-in 20 (54.1%) patients. Early and persistent symptoms in all patients were marked muscle weakness, in 78.4% of patients dizziness, in 83.8% of patients difficulty walking and unsteadiness of gait. In 34 (91.9%) patients, the most pronounced symptoms were ophthalmoplegic: blurred vision, fog, flies in front of the eyes, inability to read the text. In General, up to 10 cases of botulism are registered annually in the Astrakhan region. Almost half of the patients (45.9%) have severe botulism. The disease is mostly sporadic and is associated with the use of canned vegetables and home-made mushrooms. In addition, cases of botulism associated with the use of dried fish have become more frequent in the Astrakhan region. Late hospitalization was observed in 1/3 of patients (11 (29.7%) cases) with botulism. This is due to untimely diagnosis at the pre-hospital stage and late access of patients to medical care.

Clinical cases of atypical and severe botulism

The aim of the work was to present two clinical cases of botulism: the atypical course and the severe course with late administration of heptavalent botulinum antitoxin, which still had a significant positive clinical effect and contributed to a faster recovery of patients. The modern scientific literature regarding botulism was analyzed, hospital records of patients with botulism were presented. Conclusions. Characteristic symptoms of botulism are sometimes absent, for example, the inability to read the fine print, which is a significant challenge in diagnosing the disease. Atonic tetraparesis, dysmetabolic polyneuropathy of the lower extremities may be occasionally developed as a complication of botulism. In suspected case of botulism, even with a fuzzy epidemiological anamnesis and an unusual clinical picture, a targeted, specific examination and immediate administration of antitoxins are indicated. The heptavalent botulinum antitoxin has a significant clinical effect, contributes to recovery even at the late stages of a patient hospitalization.

A Novel Surface Plasmon Resonance Biosensor for the Rapid Detection of Botulinum Neurotoxins.

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.

Public Health Burden of Botulinum Neurotoxicity: A Research Perspective to Evaluate the Antitoxin Efficacy of Thearubigin Extract of Black Tea

Botulinum toxin (BoNT), being the most poisonous substance poses a great threat to global public health as a deadly bio-weapon. BoNT/A, BoNT/B and BoNT/E serotype toxicity cause flaccid paralysis in human by blocking neurotransmitter activity. Thearubigin, a black tea extract is found to be effective in neutralizing BoNT when experimented with animal models. This hypothesis opens a new frontier of Biological Science to understand the antitoxin property of thearubigin and applying the same in large scale to prevent BoNT neurotoxicity. Individualized dosage recommendation of thearubigin extract thus represents a natural antitoxin therapy in managing severe botulism in humans.

The case of severe botulism: artificial ventilation of lungs for 127 days

Botulism is a rare but extremely severe disease being difficult to treat and often leading to the death. In this context, undoubted interest is the detailed analysis of the course of disease in a patient with severe botulism, who in the course of therapy in total (from first admission to hospital discharge) spent totally on hospital beds (considering staying in various hospital) 152 days, including in intensive care units - 145 days, out of which 127 days - on a ventilator (the first 93 days of treatment there was carried out in the mode of mechanical ventilation IPPV, the next 34 days there was carried out intermittent mechanical ventilation in mode of BiPaP).

Treatment of foodborne botulism in current clinical toxicology: authors' reply.

Dr. Zamani pointed out the role of the wholebowel irrigation (WBI) with polyethylene gly-col as an appropriate adjunctive option of gas-trointestinal decontamination in severe botu-lism poisoning. Secondly, the author underlinethe early administration of trivalent antitoxinas soon as clinical suspicion of botulism poi-soning is made.[...]

International Outbreak of Severe Botulism with Prolonged Toxemia Caused by Commercial Carrot Juice

On 8 September 2006, 3 Georgia residents presented with symptoms of food-borne botulism, a potentially fatal illness caused by Clostridium botulinum neurotoxins. Investigators reviewed medical records and interviewed patients and family members. Foods from patients' homes and samples of the implicated commercial beverage were tested for botulinum toxin and C. botulinum by standard methods. The patients presented with cranial neuropathies and flaccid paralysis; all patients required mechanical ventilation. The 3 Georgia patients had consumed carrot juice from the same bottle before illness onset. An additional case in Florida and 2 in Ontario, Canada, were subsequently identified in patients who had consumed carrot juice. Serum samples obtained from 5 patients tested positive for botulinum toxin type A-in one patient, 12 days after illness onset, and in another patient, 25 days after illness onset. Carrot juice produced by 1 manufacturer, recovered from patients' homes in Georgia, Florida, and Ontario, yielded type A toxin. The juice contained no added sugar, salt, or preservative; inappropriate refrigeration likely resulted in botulinum toxin production. This outbreak was caused by commercially produced, internationally distributed carrot juice that was contaminated with botulinum toxin. When toxemia persists, treatment for botulism should be considered even if diagnosed weeks after illness onset. The implicated pasteurized carrot juice had no barriers to growth of C. botulinum other than refrigeration; additional protective measures for carrot juice are needed to prevent future outbreaks. The US Food and Drug Administration has since issued industry guidance to reduce the risk of C. botulinum intoxication from low-acid refrigerated juices.

A subunit type of botulinum mucosal vaccine effectively induces protective immunity in non‐human primates

Mucosally infected Clostridium Botulinum produces deadly poisonous exotoxin in the aero‐digestive tract and causes botulism. In spite of its high pathogenicity, effective vaccine against C. Botulinum has not been developed. We here prepared subunit antigen, C‐terminal half of heavy chain of botulinum neurotoxin (Hc), by E. coli expression system as a botulinum mucosal vaccine. Nasally immunized Hc induced high level of botulinum neurotoxin‐specific immune responses in both systemic and mucosal compartments of non‐human primates even in the absence of any mucosal adjuvant. Furthermore, immunized non‐human primates survived without any clinical sign after challenging with 25,000 LD50 dose of botulinum neurotoxin, while non‐immunized primates caused severe botulism within 3 hours. These results clearly show that mucosal vaccination with Hc is a novel strategy for the induction of protective immunity against botulism, which is naturally occurred or stemmed from acts of bioterrorism.

Risks of erasing wrinkles: Buyer beware!

Many times when one looks back, it is easy to say “it seemed like a good idea at the time.” After all, Botox (botulinum toxin type A), has been shown to help erase skin wrinkles. The results have been great. So when a friend offers to get some of it for you, perhaps at much less cost, and even inject it for you, well, that seems like a deal that’s too good to be true. Sometimes it is. Caveat emptor in Latin means “let the buyer beware.” This might be a good subtitle of the article by Dr. Souayah and coauthors in this issue of Neurology (Souayah N, Karim H, Kamin SS, McArdle J, Marcus S. Severe botulism after focal injection of botulinum toxin. Neurology 2006;67:1855–1856). The article tells what happens when someone was treated with an inappropriate preparation of botulinum toxin, apparently by a friend. The results were disastrous. A 34-year-old woman received botulinum toxin injections for cosmetic purposes. However, the preparation was not the FDA-approved botulinum toxin type A (brand name Botox). The injected substance was apparently research-grade toxin and was bought on the Internet. Two days after the injection, the woman developed progressive shortness of breath, swallowing difficulties, double vision, and generalized weakness. By the time she was examined by a neurologist, she was totally paralyzed with the exception of a little movement of her left big toe. An attempt to limit the paralysis with serum against the toxin was too late and did not help. Electrical studies of various arm and leg muscles showed them to be totally inactive. Tests showed that the woman had extremely high levels of botulinum toxin in her blood. In fact, the authors of the article estimate that she had been given over 2,000 to 5,000 times the usual …

Severe botulism after focal injection of botulinum toxin

We report a 34-year-old woman who developed clinical botulism after the cosmetic use of an unapproved botulinum toxin type A. Electrophysiologic findings demonstrated complete denervation with complete electrical silence. She had a lengthy recovery but was able to ambulate by discharge.

Clinical spectrum of botulism.

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.

Importance of cecum inClostridium botulinum colonization of mice and relationship of organism to large bowel

Germ-free mice, tested more than two weeks after removing their cecum, were at least 104 times more resistant than controls to intestinal colonization byClostridium botulinum type A or B. Histologic examinations were done with the cecum and colon taken fromC. botulinum-monoassociated mice. Specimens from mice with severe botulism had normal appearance. In specimens from chronically monoassociated mice, the pathogen was in the lumen, but not attached to the intestine. Scanning electron microscopy suggested a possible association of the pathogen with the mucous gel lining.

Infant Botulism Type B in Central Europe

A case of moderately severe botulism was diagnosed in a 4 weeks old white female. Clostridium botulinum toxin was identified repeatedly in the infant's faeces by means of the mouse protection assay. Clostridium botulinum was isolated in pure culture from faecal material. Both the organism and the toxin were type B.The onset of illness was characterized by mild constipation, apathy, weak sucking and difficulty with swallowing. Incipient, probably aspiration, pneumonia was diagnosed at the same time. Further signs of botulism developed during hospitalization, viz. loss of head control, pooled oral secretion, weak cry, mild ptosis, reduced facial expression, generalized muscular weakness and reduced spontaneous activity. A nasogastric feeding tube was needed because the ability to suck and swallow was impaired. Immediately on admission of the infant to hospital emergency treatment was started with Ampicilin, which was followed by penicillin injections. The infant recovered in 60 days. Subsequent medical examinations demonstrated that the recovery was complete and the development normal.The case represents the first instance of infant botulism detected on the European Continent.

Botulism, type A, and treatment with guanidine

In a double-blind crossover study in which patients received placebo or active drug for varying periods, we evaluated the ability of guanidine hydrochloride (20 to 35 mg/kg per day perorally) to improve the rate of recovery in patients with moderate or severe botulism, type A, intoxication. Among 14 patients who received conventional botulism therapy, there was no improvement in recovery rate in those who received guanidine compared with the nontreated group. Individual patients in the treated group showed neither an acceleration in their rate of improvement when they received guanidine nor a regression in their progress when the drug was stopped. Individual patients, likewise, noted no subjective improvement when they received the drug compared with the placebo. Treatment with guanidine does not enhance recovery from botulism.