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Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.

Background: Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulisminfected and healthy infants as well as the dynamic changes over time through multi-omics analysis. Methods: We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series. Results: We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32. Conclusion: Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants. [ABSTRACT FROM AUTHOR]

Abstract Background Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. Case presentation To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. Conclusion This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

ABSTRACT:Audience: This oral board case is appropriate for emergency medicine residents and medical students (with senior resident assistance) on emergency medicine rotation.Introduction: Although a somewhat rare disease, infant botulism is a true pediatric emergency that carried a 90% rate of mortality prior to the development of an antitoxin.1 While botulism infections can be iatrogenic, foodborne, or involve infected wounds, infant botulism remains the most common presentation of this disease and accounts for approximately 70% of new cases annually.2 Caused by Clostridium botulinum, the inactive spores are ingested by the infant and germinate in the large intestine.3,4 The resulting neurotoxin prevents the release of acetylcholine at the presynaptic membrane which results in flaccid paralysis. Classically, the bulbar musculature is affected before somatic muscular, which results in the typical presentation of “descending paralysis.”2,5 While confirmatory testing is important, it is often delayed by more than 24 hours, making both clinical recognition and implementation of treatment before confirmatory testing of vital importance.6,7 Treatment consists of providing airway, nutritional, and hydration support in addition to administering botulinum-specific antitoxin.8,9 While patients over the age of 12 months are treated with equine botulinum antitoxin, the Food and Drug Administration (FDA) has approved a human-derived immunoglobulin treatment, Botulism Immune Globulin Intravenous (BIG-IV, ie, “Baby BIG”) for pediatric patients less than 12 months of age.1,2,6 Ordering BIG-IV is a complex and multidisciplinary process, requiring the treating physician to discuss any suspicious case with the Infant Botulism Treatment and Prevention Program (IBTPP) which is a branch of the California Department of Public Health.6 With early recognition and implementation of treatment, most infants will make a full recovery.Educational Objectives: At the end of this oral board session, examinees will: 1) demonstrate an ability to obtain a complete pediatric medical history, 2) perform an appropriate physical exam on a pediatric patient, 3) investigate a broad differential diagnosis for neuromuscular weakness in a pediatric patient, 4) recognize the classic presentation of infant botulism and implement treatment with botulinum specific antitoxin before confirmatory testing, 5) recognize impending airway failure and intubate the pediatric patient with appropriately dosed medications and ET tube size, and 6) demonstrate effective communication with healthcare team members and parents.Educational Methods: This oral board case followed the standard American Board of Emergency Medicine- style case in a tertiary care hospital with access to all specialists and resources needed. This case was tested using 12 resident volunteers ranging from PGY 1-2 in an ACGME (Accreditation Council for Graduate Medical Education) accredited emergency medicine residency program. Learners were debriefed immediately after the case and were given the opportunity to provide feedback.Research Methods: The learners participating in the oral board case provided immediate feedback both by verbal discussion and via a written survey requiring them to rate the efficacy of the exercise. The efficacy of the educational content was assessed by comparing scoring measures of the ACGME core competencies across all learners based on post graduate year (PGY). Scoring measures were determined using a scale from 1-8, with 1-4 being unacceptable performance and 5-8 being acceptable. Efficacy required full completion of the oral board case by the residents as well as a debriefing session during which key educational concepts were discussed.Results: The practice oral board candidates consisted of 7 PGY1 and 5 PGY2 level residents. The average score of participating residents for each training level was PGY1: 4.5 and PGY2: 5.7. All except for 2 PGY2 residents missed at least one critical action with the majority of PGY1 residents missing more than one critical action for the case. All participating residents rated the educational value of the case as 4.75 (1-5 Likert scale, with 5 being excellent).Discussion: The educational content of this oral board case and debriefing session were effective for teaching the presentation, evaluation, and appropriate management of infant botulism. Infant botulism is a true pediatric emergency and prompt recognition and treatment is imperative in order to decrease mortality. While mortality was approximately 90% one hundred years ago, today infant botulism carries a much better prognosis due to the advent of antitoxin treatment with a mortality closer to 15%.1 This case highlights several classic physical exam findings including bulbar findings in addition to somatic weakness. Additionally, this case requires definitive airway management with endotracheal intubation, which is true for approximately 50% of infants with botulism.1 While a stool culture or direct toxin assay of the gastric contents, serum, or stool should be performed to confirm the diagnosis, these tests are often performed by the state health department or the Centers for Disease Control (CDC) and often take up to five days to result, during which time the patient will continue to deteriorate. Therefore, the treating physician should seek emergent consultation with the IBTPP to help facilitate the multidisciplinary decision to initiate treatment with human-derived anti-botulinum toxin antibodies.6 If the IBTPP deems that infant botulism is highly suspected based on the history and physical exam, then appropriate treatment should not be delayed and BIG-IV should be administered.6, 7 With early recognition and implementation of treatment, most infants will make a full recovery within several months to a year. Upon discharge, patients will likely require outpatient neurology follow-up in addition to physical therapy to aid in recovery. Because infant botulism is a true pediatric emergency with potentially high mortality, reaching the appropriate diagnosis expeditiously will allow the emergency physician to communicate effectively with worried parents regarding the disease progression and facilitate correct treatment early in order to prevent significant sequela.Topics: Pediatric weakness, pediatric neurotoxin, infant botulism, neuromuscular weakness.

Background: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. Case presentation: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. Conclusion: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies. [ABSTRACT FROM AUTHOR]

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007–2021. A total of 8 cases were reported during the study period. During 2019–2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March–July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.

Background: Botulism is a low incidence but potentially fatal infectious disease caused by neurotoxins produced mainly by Clostridium botulinum. There are different routes of acquisition, food-borne and infant/intestinal being the most frequent presentation, and antitoxin is the treatment of choice in all cases. In Spain, botulism is under surveillance, and case reporting is mandatory. Methods: This retrospective study attempts to provide a more complete picture of the epidemiology of botulism in Spain from 1997 to 2019 and an assessment of the treatment, including the relationship between a delay in antitoxin administration and the length of hospitalization using the Cox proportional hazards test and Kruskal–Wallis test, and an approach to the frequency of adverse events, issues for which no previous national data have been published. Results: Eight of the 44 outbreaks were associated with contaminated commercial foods involving ≤7 cases/outbreak; preserved vegetables were the main source of infection, followed by fish products; early antitoxin administration significantly reduces the hospital stay, and adverse reactions to the antitoxin affect around 3% of treated cases. [ABSTRACT FROM AUTHOR]

Clostridium botulinum causes infant botulism by colonising the intestines and producing botulinum neurotoxin in situ. Previous reports have linked infant botulism cases to C. botulinum spores in household dust, yet the baseline incidence of C. botulinum spores in residential households is currently unknown. Vacuum cleaner dust from 963 households in 13 major Canadian cities was tested for C. botulinum using a novel real-time PCR assay directed against all known subtypes of the botulinum neurotoxin gene. None of the samples tested positive for C. botulinum. Analysis of a random subset of samples by MALDI Biotyper revealed that the most common anaerobic bacterial isolates were of the genus Clostridium and the most common species recovered overall was Clostridium perfringens. Dust that was spiked with C. botulinum spores of each toxin type successfully produced positive real-time PCR reactions. These control experiments indicate that this is a viable method for the detection of C. botulinum spores in household dust. We make several recommendations for future work that may help discover a common environmental source of C. botulinum spores that could lead to effective preventative measures for this rare but deadly childhood disease. [ABSTRACT FROM AUTHOR]

Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.

A case of infant botulism of unknown origin, not involved in honey consumption, occurred in Osaka, Japan in 2020. A Clostridium botulinum type B strain named Osaka2020 was isolated from a stool sample of the patient. To clarify the epidemiology of the case, we performed whole-genome sequencing (WGS) of the isolate and compared it with strains from other sources. WGS analysis revealed that isolate Osaka2020 was classified into ST133 of a new sequence type, B5 subtype, and its toxin gene was encoded in a ∼274 kb plasmid. This plasmid was closely related to the pCLJ plasmid from strain 657Ba in the USA, reported to be conjugatively transferable to other strains. Moreover, isolate Osaka2020 also possesses another smaller plasmid that was common with some type A(B) infant botulism isolates in Japan. The phylogenetic tree from whole-genome SNP analysis showed that isolate Osaka2020 was the most closely related to a type B infant botulism isolate that occurred in Japan 10 years ago. Although no epidemiological connection among the two cases was confirmed, there is possibility that the cases are attributed to common causes such as some environmental substance. [ABSTRACT FROM AUTHOR]

Objective Laboratory investigation was performed on a suspected case of infant botulism. Methods Thirty samples of stool, left-over food and environment swabs related to the case were collected, Clostridium spp. isolation, identification and toxicity determination by mouse assay were carried out, and toxin production for isolate was conducted. Results Mice injected with the stool culture supernatant showed the typical signs of botulism including irritable, dyspnea, bellows breathing and quadriplegia followed by death. The toxicity of the stool culture supernatant was enhanced after the treatment by trypsinization but ceased after being heated at 100℃. The polyvalent antibody against botulinum neurotoxins (BoNTs) and the monovalent antibody against BoNT type E could protect mice from death. One gram-positive Clostridium isolate was cultured from infant stool sample. The morphology of the colony on the Columbia blood agar plate showed characteristics of irregular, translucent and flat with rootlike growth. It was positive for type E BoNT-encoding gene and identified as C. butyricum by 16S rRNA sequencing. Toxin production test illustrated that the C. butyricum isolate could produce type E BoNT. Conclusion This was an infant botulism caused by type E BoNT-producing C. butyricum.

Background: Botulism is a low incidence but potentially fatal infectious disease caused by neurotoxins produced mainly by Clostridium botulinum. There are different routes of acquisition, food-borne and infant/intestinal being the most frequent presentation, and antitoxin is the treatment of choice in all cases. In Spain, botulism is under surveillance, and case reporting is mandatory. Methods: This retrospective study attempts to provide a more complete picture of the epidemiology of botulism in Spain from 1997 to 2019 and an assessment of the treatment, including the relationship between a delay in antitoxin administration and the length of hospitalization using the Cox proportional hazards test and Kruskal–Wallis test, and an approach to the frequency of adverse events, issues for which no previous national data have been published. Results: Eight of the 44 outbreaks were associated with contaminated commercial foods involving ≤7 cases/outbreak; preserved vegetables were the main source of infection, followed by fish products; early antitoxin administration significantly reduces the hospital stay, and adverse reactions to the antitoxin affect around 3% of treated cases.

Background: Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum . However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum . Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis., Methods: We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series., Results: We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0 C. botulinum isolates from the patients were typed into ST31 and ST32., Conclusion: Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Wang, Teng, Luo, Sun, Huang, Hu, Xu and He.)

Botulism, a rare life-threatening toxemia, is probably underdiagnosed in all of its forms in Africa. This study reports the first laboratory-supported case of infant botulism on the African continent. A 10-week-old, previously well infant presented with progressive global weakness, feeding difficulty, and aspiration pneumonia. During a lengthy hospitalization, a rare bivalent Clostridium botulinum strain, producing subtype B3 and F8 toxins and with a new multilocus sequence type, was isolated from stool. The infant was successfully treated with a heptavalent botulinum antitoxin infusion and pyridostigmine. Despite the relative rarity of infant botulism, this case illustrates the importance of maintaining a high level of clinical suspicion when assessing hypotonic infants. The value of modern diagnostic modalities in identifying and characterizing this under-recognized condition is also demonstrated.

Infant botulism (IB) is defined as a potentially life-threatening neuroparalytic disorder affecting children younger than 12 months. It is caused by ingestion of food or dust contaminated by Clostridium botulinum spores, which germinate in the infant's large bowel and produce botulinum neurotoxin. Although the real impact of IB is likely underestimated worldwide, the USA has the highest number of cases. The limited reporting of IB in many countries is probably due to diagnostic difficulties and nonspecific presentation. The onset is usually heralded by constipation, followed by bulbar palsy, and then by a descending bilateral symmetric paralysis; ultimately, palsy can involve respiratory and diaphragmatic muscles, leading to respiratory failure. The treatment is based on supportive care and specific therapy with Human Botulism Immune Globulin Intravenous (BIG-IV), and should be started as early as possible. The search for new human-like antibody preparations that are both highly effective and well tolerated has led to the creation of a mixture of oligoclonal antibodies that are highly protective and can be produced in large quantities without the use of animals. Ongoing research for future treatment of IB involves the search for new molecular targets to produce a new generation of laboratory-produced antitoxins, and the development of new vaccines with safety and efficacy profiles that can be scaled up for clinical use. This narrative literature review aims to provide a readable synthesis of the best current literature on microbiological, epidemiological and clinical features of IB, and a practical guide for its treatment. [ABSTRACT FROM AUTHOR]

Infant botulism is a rare and life-threatening disease caused by the inhalation of Clostridium botulinum spores and differs from adult forms. We report the case of infant botulism in a 4-month-old boy who was exclusively breastfed without any consumption of honey. He presented with severe and acute encephalo-myelo-radiculitis. The patient was treated without success for suspected "postviral" central nervous system inflammatory disease. The diagnosis was eventually made 20 days after the onset of symptoms on the basis of a stool sample. Recovery was complete. Infant botulism should be suspected when infants present with acute flaccid paralysis or brainstem weakness and specific immunoglobulins should be administered. [ABSTRACT FROM AUTHOR]

We present the closed genome sequence of the Clostridium botulinum BT-22100019 strain isolated from the stool specimen of an infant diagnosed with botulism. With 4.33-Mb genome size and 28.0% G + C content, the bont/B1 gene encoded for botulinum neurotoxin serotype B was found on a 262 kb plasmid arranged in a ha + orfx - cluster., Competing Interests: The authors declare no conflict of interest.

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature.

Abstract Infant botulism was rarely reported in China. The second reported event of the disease including three cases occurred in 2015. In the present study, one (the third case) of the three cases was identified and investigated to trace the sources of transmission. Samples from feces and foodstuffs were used to isolate Clostridium botulinum strains. Each isolate was obtained from the baby's feces and opened powdered infant rice cereal, respectively. In this case, the C. botulinum strains were identified and characterized by combined mouse bioassay, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and high-throughput sequencing including single nucleotide polymorphisms (SNP). Results showed that the disease was caused by a type B strain of C. botulinum. Strains associated with this case as well as isolates from stored and historical samples were phylogenetically analyzed and compared. C. botulinum type B isolates from the infant feces and from an opened container of infant rice cereal were indistinguishable, suggesting that opened container of infant rice cereal is likely to be the source of transmission of spores to the infant. It is not clear that how the opened container was contaminated and the child was exposed since environmental testing was not performed. This study provides detailed information about usage of the three methods and references for dealing with other associated cases. Highlights • An Infant Botulism Case was investigated. • The disease was caused by a type B strain of C. botulinum. • Mouse lethality assay, MALDI-TOF MS and high-throughput sequencing were used. • The opened container of rice cereal is likely to be the source for transmission. [ABSTRACT FROM AUTHOR]

• The first laboratory-confirmed case of infant botulism in Africa. • Clostridium botulinum is a rare cause of flaccid paralysis in infants. • Bivalent C. botulinum strain, producing subtype B3 and F8 toxins. • A new sequence type (ST121), with novel alleles for two loci (hsp and oppB). • Successful treatment with heptavalent equine antitoxin and pyridostigmine. Botulism, a rare life-threatening toxemia, is probably underdiagnosed in all of its forms in Africa. This study reports the first laboratory-supported case of infant botulism on the African continent. A 10-week-old, previously well infant presented with progressive global weakness, feeding difficulty, and aspiration pneumonia. During a lengthy hospitalization, a rare bivalent Clostridium botulinum strain, producing subtype B3 and F8 toxins and with a new multilocus sequence type, was isolated from stool. The infant was successfully treated with a heptavalent botulinum antitoxin infusion and pyridostigmine. Despite the relative rarity of infant botulism, this case illustrates the importance of maintaining a high level of clinical suspicion when assessing hypotonic infants. The value of modern diagnostic modalities in identifying and characterizing this under-recognized condition is also demonstrated. [ABSTRACT FROM AUTHOR]

Botulism is a rare but severe disease which is characterized by paralysis and inhibition of secretions. Only a few cases had been reported at the end of the 19th century in France. The disease was frequent during the second world war, and then the incidence decreased progressively. However, human botulism is still present in France with 10–25 cases every year. Food-borne botulism was the main form of botulism in France, whereas infant botulism (17 cases between 2004 and 2016) was rare, and wound and inhalational botulism were exceptional. Type B was the prevalent botulism type and was mainly due to consumption of home-made or small-scale preparations of cured ham and to a lesser extent other pork meat products. In the recent period (2000–2016), a wider diversity of botulism types from various food origin including industrial foods was reported. Severe cases of type A and F botulism as well as type E botulism were more frequent. Albeit rare, the severity of botulism justifies its continued surveillance and recommendations to food industry and consumers regarding food hygiene and preservation practices.

Infant botulism is a progressive process described as starting with descending weakness, facial palsies and constipation. Loss of bulbar reflexes and flaccid paralysis are common in infants less than 6 months old who have infant botulism. Clostridium botulinum, the bacteria that produce the toxin that causes this condition, are ubiquitous in the United States including Hawai'i, but infant botulism is rarely reported here. This report describes 2 cases of infant botulism with atypical initial presentations diagnosed on O'ahu, Hawai'i. Patient A is a 3-month-old male who presented with altered mental status, including inconsolability, who progressed to loss of gag reflex and constipation. Due to early concern for meningitis, Patient A was treated with antibiotics, however further evaluation led to eventual positive testing for botulinum B toxin. Patient B is a 2-month-old female who presented with somnolence and fever after immunizations and progressed to respiratory failure and apparent dehydration. Because she presented shortly after receiving immunizations, metabolic disorders were strongly considered as a potential cause of symptoms, but Patient B had normal metabolic evaluation and eventually tested positive for botulinum A toxin. Altered mental status and fever are unusual presentations for infant botulism. Infant botulism should be considered in infants with altered mental status when the course of illness includes the development of constipation and weakness, and evaluations are not suggestive of alternative causes, including infection, metabolic diseases, and spinal muscular atrophy. Early consideration and treatment of infant botulism should be considered for infants presenting with altered mental status who develop neuromuscular weakness. The Infant Botulism Treatment and Prevention Program (www.infantbotulism. org) should be contacted early for assistance with diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objectives We undertook an open-label, uncontrolled study of investigational recombinant botulinum vaccine for botulinum neurotoxin (BoNT) serotypes A and B (rBV A/B) to assess its safety and immunogenicity in healthy volunteers who had been previously immunized with investigational pentavalent botulinum toxoid. Study participants who wished to do so could donate their hyperimmune plasma for production of Human Botulism Immune Globulin Intravenous (BIG-IV, BabyBIG®). Study design A single 0.5 ml (mL), 40-microgram intramuscular injection of rBV A/B was administered to study participants. Post-vaccination sera collected at approximately 2-week intervals were evaluated for anti-BoNT/A and anti-BoNT/B neutralizing antibody concentrations (NAC). Local and systemic treatment-emergent adverse events (TEAEs) were identified by clinical and laboratory monitoring for 12 weeks post-vaccination with a final telephone follow-up for additional safety assessment at 6 months. The primary endpoint for immunogenicity was a ≥4-fold rise in NAC in ≥50% of participants by Week 4 post-vaccination. Results All 45 enrolled participants completed the study. Forty-two of 45 participants (93.3%) experienced at least one TEAE. Overall, 138 of 218 (63.3%) reported TEAEs were treatment-related, the majority of which were mild injection-site reactions. No serious or unexpected adverse events occurred. The study achieved its primary immunogenicity endpoint with 37/45 (82.2%) participants and 39/45 (86.7%) participants having a ≥4-fold rise in NAC to anti-BoNT/A and to anti-BoNT/B, respectively, by Week 4 post-vaccination. Conclusion A single 0.5 mL dose of rBV A/B was safe, well-tolerated and immunogenic in participants previously immunized with pentavalent botulinum toxoid. The tolerability and immunogenicity characteristics of rBV A/B vaccination of individuals with existing BoNT immunity support its potential future use to provide occupational protection to botulism laboratory workers. Almost all study participants donated hyperimmune plasma for production of BIG-IV. ClinicalTrials.gov registration number: NCT01701999. [ABSTRACT FROM AUTHOR]

Objectives: To report the efficacy of Human Botulism Immune Globulin Intravenous (BIG-IV) in the first 12 years following its licensure in 2003 and to characterize its use nationwide in treating patients with infant botulism.Study Design: Medical records and billing information were collected for US patients treated with BIG-IV from 2003 to 2015. Length of hospital stay (LOS) and hospital charge information for treated patients were compared with the BIG-IV Pivotal Clinical Trial Placebo Group to quantify decreases in LOS and hospital charges.Results: The use of BIG-IV reduced mean LOS from 5.7 to 2.2 weeks. This shortened hospital stay resulted in a mean decrease in hospital charges of $88 900 per patient. For all US patients 2003-2015, total decreases in LOS and hospital charges were 66.9 years and $86.2 million, respectively. The decrease in mean LOS was time dependent: BIG-IV treatment on hospital days 0-3 reduced mean LOS by 3.7 weeks (P <.001 vs the BIG-IV Pivotal Clinical Trial Placebo Group), on hospital days 4-7 by 2.6 weeks (P <.001 vs the BIG-IV Pivotal Clinical Trial Placebo Group) and on hospital days 8-10 by just 1 week (P = NS). Since licensure, 1192 patients in 48 states and Washington, DC, have been treated with BIG-IV.Conclusions: The use of BIG-IV since its licensure in 2003 treated approximately 93% of US patients with laboratory-confirmed infant botulism, and prevented >65 years in hospital stay and >$85 million in hospital charges from occurring. The greatest LOS reduction was achieved when BIG-IV was administered soon after hospital admission. Effective and appropriate use of BIG-IV in the US has continued in the postlicensure period. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the actual diagnoses of 76 patients (2005-2015) whose clinical presentations so closely resembled infant botulism that the patients were treated with Human Botulism Immune Globulin Intravenous (BIG-IV; BabyBIG), but whose illnesses subsequently were not laboratory confirmed as infant botulism ("clinical mimics" of infant botulism).Study Design: The California Department of Public Health produces BIG-IV and distributes it nationwide as a public service (ie, not-for-profit) orphan drug to treat patients hospitalized with suspected infant botulism. During the study period, admission records and discharge summaries for all patients treated with BIG-IV but who lacked a laboratory-confirmed diagnosis of infant botulism were collected and abstracted. The patients' discharge diagnoses were identified, categorized, and compared with previously reported clinical mimics categories for 32 patients (1992-2005).Results: From 2005 to 2015, 76 clinical mimic illnesses were identified. These illnesses were distributed into the 5 categories previously reported of (1) probable infant botulism lacking confirmatory testing (26.3%); (2) spinal muscular atrophy (19.7%); (3) miscellaneous (15.8%); (4) metabolic disorders (11.8%); and (5) other infectious diseases (10.6%). Of the 76 clinical mimic illnesses, 15.8% had no alternate diagnosis established and were therefore categorized as undetermined.Conclusions: Over the 23 years 1992-2015, patients presenting with illnesses so clinically similar to infant botulism that they were treated with BIG-IV had actual diagnoses that were distributed into 5 main categories. These categories and their individual components constitute a working bedside differential diagnosis of infant botulism. [ABSTRACT FROM AUTHOR]

Abstract Background Though botulism is a rare disease overall, all infants younger than 1 year of age are at risk of contracting infant botulism, the most prevalent form reported in the United States. Nonetheless, infant botulism is frequently omitted from the differential diagnosis of the very young neonate exclusively due to age, and the diagnosis is often only considered secondarily after a costly and prolonged work up is undertaken. Delayed diagnosis can lead not only to unnecessary testing but also to prolonged hospital stay and increased morbidity. Case This case series highlights three critically ill neonates, all younger than 30 days, who presented to our neonatal intensive care unit and were eventually diagnosed with infant botulism. The initial diagnostic dilemma is described for each of these patients and highlights the importance of early recognition of the main symptoms, in addition to consideration of important potential coinciding conditions.

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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

We present the first case of abnormal neuroimaging in a case of infant botulism. The patient presented with clinical findings of constipation, bulbar weakness and descending, symmetric motor weakness which are consistent with the classic findings of infant botulism. Magnetic resonance imaging (MRI), however, revealed restricted diffusion in the brain and enhancement of the cervical nerve roots. Traditionally, normal neuroimaging was used to help differentiate infant botulism from other causes of weakness in infants. Abnormal neuroimaging is seen in other causes of weakness in an infant including metabolic disorders and hypoxic-ischemic injury but these diagnoses did not fit the clinical findings in this case. The explanation for the MRI abnormalities in the brain and cervical nerve roots is unclear as botulinum toxin acts at presynaptic nerve terminals and does not cross the blood-brain barrier. Possible explanations for the findings include inflammation from the botulinum toxin at the synapse, alterations in sensory signaling and retrograde transport of the botulinum toxin. The patient was treated with human botulism immune globulin and had rapid recovery in weakness. A stool sample from the patient was positive for Type A Clostridium Botulinum toxin eventually confirming the diagnosis of infant botulism. The findings in this case support use of human botulism immune globulin when the clinical findings are consistent with infant botulism despite the presence of MRI abnormalities in the brain and cervical nerve roots.

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.El botulismo del lactante es una toxiinfección causada, principalmente, por Clostridium botulinum. Debido a que esta infección ocurre en el tracto intestinal, la presencia de esta bacteria y sus neurotoxinas ha sido investigada en numerosos alimentos. En muchos países se utiliza el té de tilo (Tilia spp.) como sedante natural, el que se administra incluso a los lactantes. A fin de contribuir al esclarecimiento de la transmisión de esta enfermedad, se investigó la prevalencia y la carga de esporas botulínicas en esta hierba. Se analizaron 100 muestras de tilo comercializado a granel y 100 muestras de tilo industralizado en “saquitos”. Los resultados de prevalencia fueron analizados por el test de Fisher y la carga de esporas por la técnica del número más probable. Se halló una prevalencia de esporas de C. botulinum del 3% en el tilo comercializado a granel, con una carga de 30 esporas/100 g de hierba. En tanto, ninguna de las muestras en saquitos acusó la presencia del patógeno. Se identificaron tres cepas de C. botulinum, dos tipo A y una tipo B. En virtud de estos resultados, el tilo podría considerarse un potencial vehículo de esporas de C. botulinum y la administración de sus infusiones a menores y lactantes, un riesgo para la transmisión de la enfermedad.

Infant botulism is the most common form of human botulism; however, its transmission has not been completely explained yet. Some of the most recognized potential sources of Clostridium botulinum spores are the soil, dust, honey and medicinal herbs. In Argentina, 456 cases of infant botulism were reported between 1982 and 2007. C. botulinum type A was identified in 455 of these cases whereas type B was identified in just one case. However, in Argentina, types A, B, E, F, G, and Af have been isolated from environmental sources. It is not clearly known if strains isolated from infant botulism cases have different characteristics from strains isolated from other sources. During this study, 46 C. botulinum strains isolated from infant botulism cases and from environmental sources were typified according to phenotypic characteristics. Biochemical tests, antimicrobial activity, and haemagglutinin-negative botulinum neurotoxin production showed uniformity among all these strains. Despite the variability observed in the botulinum neurotoxin's binding to cellular receptors, no correlation was found between these patterns and the source of the botulinum neurotoxin. However, an apparent geographical clustering was observed, since strains isolated from Argentina had similar characteristics to those isolated from Italy and Japan, but different to those isolated from the United States.El botulismo del lactante es la forma más común del botulismo humano; sin embargo, su forma de transmisión no ha sido totalmente explicada. El suelo, el polvo ambiental, la miel y algunas hierbas medicinales son potenciales fuentes de esporas de Clostridium botulinum. Entre 1982 y 2007 se informaron en Argentina 456 casos de botulismo del lactante, 455 casos debidos al serotipo A y uno al serotipo B. Sin embargo, los serotipos A, B, E, F, G y Af han sido aislados de suelos y otras fuentes en Argentina. No se conoce si las cepas aisladas de casos de botulismo del lactante poseen características diferentes de las cepas aisladas de otras fuentes. Durante este estudio se caracterizaron 46 cepas de C. botulinum. Las pruebas bioquímicas y de sensibilidad a los antimicrobianos y la producción de neurotoxina botulínica hemaglutinina-negativa mostraron uniformidad entre estas cepas. A pesar de la variabilidad observada respecto de la unión de la neurotoxina a receptores celulares, no se observó una correlación entre estos patrones de unión y la fuente de aislamiento. Sin embargo, se observó una aparente agrupación geográfica, ya que las cepas aisladas en Argentina tuvieron características similares a las observadas en las cepas aisladas en Italia y Japón, pero diferentes de las que se registraron en las cepas aisladas en los Estados Unidos.

O botulismo infantil tem afetado crianças abaixo de um ano de idade em várias regiões do mundo, e o mel tem sido identificado como uma das mais importantes fontes de intoxicação alimentar. Apesar disso, há dados escassos sobre o botulismo entre crianças no Brasil, especialmente no tipo de alimento comercial mais implicado nesta patologia. Este estudo pretendeu investigar a presença de esporos de Clostridium botulinum em mel comercializado no Brasil. Cem amostras de mel comercializado em seis diferentes Estados brasileiros (SP, MG, GO, CE, MT, SC) foram pesquisados para a presença de esporos de Clostridium botulinum, usando o choque térmico, seguido pela inoculação em caldo Cooked Meat Medium (Difco®) e incubado em condições anaeróbias. As culturas positivas foram analisadas através de esfregaços corados pelo Gram e semeadas em placas de Reinforced Clostrideo Agar (Difco®) e placas de Sulfito Polimixina Sulfadiazina -SPS (Difco®), as quais foram incubadas em condições anaeróbicas para obter colônias desta bactéria. As colônias positivas foram submetidas a teste de toxicidade através da inoculação em camundongos susceptíveis e caracterização bioquímica. Foram encontradas colônias de Clostridium botulinum que produzem toxinas ativas em 7% das amostras de mel comercial, realçando a relevância deste microrganismo para a saúde pública devido ao alto risco potencial de o mel comercializado nestas regiões brasileiras causar o botulismo infantil, especialmente em crianças abaixo de um ano de idade.Infant botulism has been affecting children under one year of age in several regions of the world and honey has been identified as one of the most important source of this food borne disease. Despite this, there are scarce data about botulism among children in Brazil, specially the type commercial food most implicated in this pathology. This study aimed at investigating the presence of spores of Clostridium botulinum in honey commercialized in Brazil. One hundred of honey samples commercialized in six different Brazilin states (SP, MG, GO, CE, MT, SC) were searched for the presence of spores of Clostridium botulinum, using thermal shock followed by the inoculation in Cooked Meat Medium (Difco®) and incubation in anaerobic conditions. The positives cultures were analyzed by Gram stain and seeded in Reinforced Clostrideo Agar (Difco®) and Sulfito Polimixina Sulfadiazina -SPS (Difco®) plates, which were incubated in anaerobic conditions in order to pick up the colonies of this bacteria. The positive colonies were submitted to toxicity test by inoculation in susceptible mice and to biochemical characterization. Clostridium botulinum colonies producing actively toxins were detected in 7% of the commercial honey samples, highlighting the relevance of this microorganism for public health due to the high potential risk of honey commercialized in these Brazilian regions to cause Infant Botulism, specially in children under one-year old.

O botulismo alimentar ocorre pela ingestão de toxinas pré-formadas pelo Clostridium botulinum, consideradas as mais potentes dentre as toxinas conhecidas. Caracteriza-se como uma doença de extrema gravidade, de evolução aguda, provoca distúrbios digestivos e neurológicos, em conseqüência à ingestão de diversos tipos de alimentos. As conservas caseiras estão entre os alimentos que oferecem maior risco à população consumidora. Os produtos de origem animal são frequentemente associados aos surtos da doença, destacando-se os embutidos, tais como salsichas, salames, presuntos e patês. Derivados do leite e enlatados, bem como produtos fermentados, são passíveis de provocar a intoxicação. As outras formas naturais da doença são botulismo por feridas e botulismo infantil, normalmente associado ao consumo de mel contendo esporos do Clostridium botulinum.Foodbourne botulism occurs after ingestion of preformed toxins produced by the Clostridium botulinum, which has been considered one of the most potent known one. The disease, acquired after ingestion of various kinds of foods, has acute character, and provokes gastrointestinal and neurologic symptoms. Homemade canned foods are those that represent higher risk to human health. Processed meat products are frequently associated with botulism outbreaks, mainly sausages, ham and pates. Dairy and canned food, as well as fermented foods, also may be related with this disease. Still, botulism may be caused by toxin production in deep wound, named wound botulism; and after ingestion of honey contaminated with spores by infants, named infant botulism.

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007-2021. A total of 8 cases were reported during the study period. During 2019-2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March-July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.