Botulism Research Articles

Epidemiological investigation of acute poisoning inpatients in a tertiary hospital in Xinjiang: a retrospective analysis of 10 years

Objective To improve the clinical prognosis of patients by reviewing ten years epidemiology data of acute poisoning inpatients. Methods The epidemiology data of the acute poisoning inpatients from 2006-2015 were retrospectively analyzed. The indexes including age, gender, nationality, geographical distribution, substance of poison, seasons, diagnosis and fee-for-service were collected. Results There were 1 083 patients with acute poisoning in total, 624 cases (57.6%) for gas poisoning, 213 cases (19.7%) for pesticide poisoning, 136 cases (12.6%) for drug poisoning, 74 cases (6.8%) for food poisoning and 36 cases for others. The ration of male to female was 0.94∶1. The age of 31 to 45 range accounted for the highest proportion. The incidence of poisoning in 2011-2015 was significantly higher than that in 2006-2010 (P<0.05). The geographical distribution was also significantly different (P<0.05), most of the cases were in Shihezi city, then were Manasi and Sawan counties. Among the 1 083 patients, 59% cases were cured, 33.6% cases were improved after treatment, and the mortality rate was 2.6%. Fee-for-service was also significantly increased in the older patients or males, and substance of poisoning dependent. The highest treatment cost was carbon monoxide poisoning, then were pesticide, drugs and food. Conclusions The common causes of poisoning in Shihezi city were carbon monoxide, organophosphorus pesticide, botulism and drugs, more emergency medical service should prevent poisoning and treat these patients. Key words: Acute poisoning; Hospitalized patients; Epidemiological characteristics

Botulinum neurotoxin type B uses a distinct entry pathway mediated by CDC42 into intestinal cells versus neuronal cells.

Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT type B (BoNT/B) most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonisation such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa. Here, we investigated the entry pathway of BoNT/B using fluorescent C-terminal domain of the heavy chain (HcB), which is involved in the binding to specific receptor(s) and entry process into target cells. While the combination of gangliosides GD1a /GD1b /GT1b and synaptotagmin I and to a greater extent synaptotagmin II constitutes the functional HcB receptor on NG108-15 neuronal cells, HcB only uses the gangliosides GD1a /GD1b /GT1b to efficiently bind to m-ICcl2 intestinal cells. HcB enters both cell types by a dynamin-dependent endocytosis, which is efficiently prevented by Dynasore, a dynamin inhibitor, and reaches a common early endosomal compartment labeled by early endosome antigen (EEA1). In contrast to neuronal cells, HcB uses a Cdc42-dependent pathway to enter intestinal cells. Then, HcB is transported to late endosomes in neuronal cells, whereas it exploits a nonacidified pathway from apical to basal lateral side of m-ICcl2 cells supporting a transcytotic route in epithelial intestinal cells.

Effective treatment of infant botulism on day 13 after symptom onset with human botulism antitoxin

Effective treatment of infant botulism on day 13 after symptom onset with human botulism antitoxin

Trends in Outcomes and Hospitalization Charges of Infant Botulism in the United States: A Comparative Analysis Between Kids' Inpatient Database and National Inpatient Sample

BackgroundNew 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. MethodsWe 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. ResultsBetween 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. ConclusionInfant 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.

Neurotoxins from Clostridium botulinum (serotype A) isolated from the soil of Mendoza (Argentina) differ from the A-Hall archetype and from that causing infant botulism

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.

Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes.

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.

A penicillin- and metronidazole-resistant Clostridium botulinum strain responsible for an infant botulism case

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.

Stimulated jitter analysis for the evaluation of neuromuscular junction disorders in children.

Stimulated jitter analysis (stim-JA) using a concentric needle electrode is a technique used to study the neuromuscular junction (NMJ) without voluntary activation. Our objective was to study the diagnostic sensitivity, specificity, and feasibility of stim-JA in infants and children with suspected NMJ defects. Sixteen infants and young children ages 2 months to 17 years with suspected NMJ disorders were evaluated using stim-JA over a period of 12 months. Subjects with suspected NMJ defects and abnormal stim-JA subsequently had laboratory confirmation of myasthenia gravis (n = 5) and infant botulism (n = 2). Turnaround time for confirmatory laboratory tests was 6.0 ± 4.3 days, whereas stim-JA results were available immediately. All subjects tolerated stim-JA well without complications or need for sedation. Stim-JA is a sensitive and safe first-line diagnostic test for evaluation of suspected pediatric NMJ disorders. Stim-JA results precede assay results and may guide early treatment.

Characterizing the fecal microbiota of infants with botulism.

BackgroundInfant 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.ResultsSeven 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.ConclusionsSignificant 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.

Inhibition of botulinum neurotoxins interchain disulfide bond reduction prevents the peripheral neuroparalysis of botulism

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 100kDa chain which binds to the presynaptic membrane and assists the translocation of a 50kDa 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.

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FigureFigureFigureA 5-month-old boy with no notable medical history presented with weakness, poor feeding, and constipation. His poor feeding had gradually progressed over two weeks: he would tire easily and cough when trying to swallow. He had had constipation for seven to eight days, and had grown progressively weaker, now unable to lift his head off the bed. His family denies fever, vomiting, focal weakness, and seizure-like activity. Vaccinations are up to date, and his mother said he was born full-term through an uncomplicated vaginal delivery. The family lives on a farm with various livestock. Find the diagnosis and case discussion on p. 16. Diagnosis: Infant Botulism Unlike its better-known brethren, foodborne botulism, which is caused by the ingestion of preformed botulin toxins in tainted foods (e.g., home canning), infant botulism is caused by the ingestion of the entire Clostridium botulinum spore. Most commonly seen between the first and sixth month of life, infant botulism, though rare, can be life-threatening. The C. botulinum spores colonize the infant's intestinal tract, allowing the toxin to be produced. This potent toxin prevents the release of multiple neurotransmitters, most notably acetylcholine, and the blockage of these cholinergic synapses causes a symmetric, descending motor weakness and flaccid paralysis with autonomic dysfunction. (BMC Microbiol 2010;10:267.) Infants are at increased risk because studies have shown that the absence of competitive microbial flora enables the growth of the ingested spores. (Clin Microbiol Rev 2006;19[2]:298.) As a result, infants, who have not yet become colonized with normal gut flora, are at high risk of becoming colonized with the botulinum spores. (Clin Microbiol Rev 2006;19[2]:298.) Despite its common association with honey, C. botulinum is actually most often linked to soil and dust exposure. Living in a rural area and with someone who works with soil are risk factors for bacterial colonization. (Pediatr Neurol 2005;32[3]:149.) The first clinical symptom of infant botulism is constipation. Infants then experience loss of head control (from weakness of the neck muscles), followed by symmetric, descending hypotonia and weakness, ultimately progressing to involve the diaphragmatic muscles. (Annu Rev Med 1980;31:541.) Infant botulism is distinguished from other neurological disorders by the presence of symmetric cranial nerve palsies. These include ptosis, fatigable pupillary response to light, ophthalmoplegia, poor suck, decreased gag reflex, difficulty swallowing, and expressionless facies. (Pediatrics 2007;119[4]:826.) Diagnosis of infant botulism is achieved via bioassay, and this study unsurprisingly may take many days to return, leaving the treatment team with the dilemma of treating without a conclusive diagnosis. This is complicated even more so because the definitive treatment, intravenous botulism immunoglobulin (BabyBIG), is only available through the California Department of Public Health, so infant botulism remains a clinical diagnosis. Supportive care should pay special attention to airway protection, whether there is a need for mechanical ventilation, positioning to decrease aspiration risks, and urinary retention. This patient was admitted to the PICU to monitor his airway while awaiting BabyBIG, which was administered the following day. Two weeks later, the immunoassay returned positive for botulism toxin, and he made a full recovery. Differential Diagnosis for Infant Weakness Sepsis Electrolyte abnormalities Meningitis Botulism metabolic abnormalities Muscular dystrophies Myasthenia gravis Spinal cord trauma Share this article on Twitter and Facebook. Access the links in EMN by reading this on our website or in our free iPad app, both available at www.EM-News.com. Comments? Write to us at [email protected].

Relationship between the incidence of infant botulism and the presence of botulinum-toxin producing clostridia in the soil of Argentina from 1982–2005

Infant botulism is the most common form of human botulism in some countries including Argentina. However, its transmission has not been completely elucidated. In Argentina, 366 laboratory-confirmed infant botulism cases were reported between March 1982 and December 2005. The average annual incidence was 2.2 per 100,000 live births. All 108 cases diagnosed in our laboratory had botulinum toxin producing organisms in their feces, 96.3% also had botulinum toxin in feces, and 69% had detectable botulinum toxin in their serum. Biochemical tests showed uniformity among the botulinum toxin-producing clostridia isolated from infant botulism cases and soil samples. A positive relationship between presence of botulinum spores in soil and illness incidence was observed in the Northeast and West regions but not in the Central, South and Northwest regions. In the Northwest and Central regions, there was a relatively high occurrence of botulinum spores in the soil but low incidence of the disease. Type A botulinum toxin was detected in all infant botulism cases and also it was the toxin type most prevalent in the soil. Despite the presence of B and F types in the soil, there were no reports of infant botulism cases by these types in Argentina between 1982 and 2005.

Severe infant botulism with cardiac arrest

Botulism is caused by the toxin produced by Clostridium botulinum. This toxin binds the peripheral presynaptic cholinergic membranes, preventing the release of acetylcholine and thereby producing a life-threatening, paralytic illness. We report the case of an infant with botulism who proceeded to cardiorespiratory arrest, but whose outcome was very satisfactory, in spite of the delay in diagnosis.

Infant botulism manifesting in an exclusively breast-fed patient: A case report

Infant botulism manifesting in an exclusively breast-fed patient: A case report

Biphasic botulism diagnosed by electromyogram

Botulism is an acute, flaccid paralytic illness caused by the neurotoxin produced by Clostridium species . Three forms of botulism are known; infant botulism, food borne, and wound botulism. We report an 11-year-old boy with food borne botulism diagnosed on electromyography. Although his clinical findings improved in 10 days, his symptoms recurred, showing a biphasic course. After 3 weeks, he was symptom free. His electromyography findings were also normal on the 3rd week. After 3 weeks, he was discharged without clinical symptoms.

First Report of an Infant Intestinal Botulism Case in A Recent Decade in Taiwan

On 20^(th) January 2015, a 5-month-old girl was notified, and later known as a laboratory-confirmed infant botulism in a medical center in Tainan. It is the first report of an infant intestinal botulism patient in Taiwan in the recent decade. As the tests to the five suspicious food samples were all negative, the source of infection remains uncertain. There are a number of experiences to be shared from the investigation: 1. Blood draws in infants are limited so that it would have taken more than once to collect blood samples from an infant for Botulism tests; 2. Since only Equine Botulinum Antitoxin is available in Taiwan, clinicians should balance between potential risk of hypersensitivity and therapeutic outcome. Accordingly, the workbook provided by Taiwan CDC on prevention and control of infant botulism might need to be amended; 3. In order to collect epidemiological data, it is very important to support family members psychologically, as they feel sorry and guilty for the incidence.

Anaerobic infections in children

Anaerobic bacteria commonly cause infection in children. Anaerobes are the most predominant components of the normal human skin and mucous membrane bacterial flora, and are therefore a common cause of bacterial infections of endogenous origin. Because of their fastidious nature, they are difficult to isolate from infectious sites and are often overlooked. Anaerobic infections can occur in all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. Anaerobic bacteria colonize the newborn after delivery and have been recovered from several types of neonatal infections. These include cellulitis of the site of fetal monitoring, neonatal aspiration pneumonia, bacteremia, conjunctivitis, omphalitis, and infant botulism. The lack of directing adequate therapy against these organisms may lead to clinical failures. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens. Treatment of anaerobic infection is complicated by the slow growth of these organisms, by their polymicrobial nature, and by the growing resistance of anaerobic bacteria to antimicrobials. Antimicrobial therapy is often the only form of therapy required, whereas in other cases it is an important adjunct to a surgical approach. Because anaerobic bacteria generally are recovered mixed with aerobic organisms, the choice of appropriate antimicrobial agents should provide for adequate coverage of both types of pathogens.

Microbiology and foodborne pathogens in honey

ABSTRACTHoney 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.

Spotting infantile botulism: a taste of molten honey

Abstract Infant botulism is a serious and life threatening disease and is the commonest form of botulism. Whilst it is rare outside the USA sporadic cases continue to be reported from other parts of the world. It is important to have a high index of suspicion for accurate and early diagnosis as the clinical manifestations are varied. Treatment with botulinum immunoglobulin may modify the outcome of this condition with more rapid recovery from respiratory paralysis and overall decreased intensive care stay.

Consumers' Perception and Knowledge of Food Safety: Results of Questionnaires Accessible on IZSalimenTO Website.

The present survey was undertaken to investigate consumers’ knowledge of the main foodborne agents and dietary regimen during pregnancy. Data were collected using monthly questionnaires available on IZSalimenTO website between March 2013 and January 2014. Hepatitis A virus questionnaire: 20 respondents (77%) recognized berries as foodstuff linked to the outbreak of hepatitis A. The majority correctly indicated as precautionary advice to boil berries before consumption. Botulism questionnaire: 29 respondents (62%) indicated pesto as food involved in botulism alert in July 2013. The risk of infant botulism in infant less than 1 year old due to honey consumption is known by 24 respondents (51%). Main foodborne disease questionnaire: the risk of infection by Salmonella after the consumption of foods made with raw eggs is known by the majority (94%; N=17) as well as the treatments to be applied in order to make fresh fish safe from parasites (76%). Pregnancy questionnaire: 20 respondents (74%) believed that washing vegetables and fruits with sodium bicarbonate or chlorate solution is able to inactivate Toxoplasma; only 4 (15%) reported both raw meat and vegetables washed with sodium bicarbonate as food at risk. Results indicate that all consumers should be trained on behaviour and dietary regimen to be adopted in pregnancy and in infant <1 year old. The website may be considered as a useful tool to assess consumers’ knowledge: both the news section and the contents published may be a source of information and education for consumers on food safety.