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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]

• 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]

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]

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]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Infant botulism (IB) is caused by the intestinal colonization by Clostridium botulinum in the first year of life and its subsequent production of neurotoxins. Traditionally, IB has been associated to honey consumption. IB cases tend to cluster in geographic regions. In Europe, IB is a rare disorder. From 1976 through 2006, 65 cases were identified in 13 European countries. In Spain, in the last 15 years, most of the cases have been reported in one region, Andalusia (Southern Spain). A specific treatment for IB type A and type B (BabyBIG) is available outside of the United States since 2005. Methods: and aims: We performed a retrospective review of IB cases detected in Andalusia since 1997 and compare them with the cases of IB reported in Europe. Results: We identified 11 confirmed cases of IB in Andalusia since 1997, and 14 cases in Spain. Nine out of 11 cases were detected since 2007; none of these infants had been exposed to honey consumption. One case in 1997 and another in 2000 were associated to honey. Two cases were treated with BabyBIG in 2007. In the period 2006–2012 the cases of IB reported in Europe were 54. Conclusions: We identified a considerable increase in the incidence of IB since 2006. A tendency to a reduction in the number of cases of IB linked to honey consumption has also been identified. An increase in the exposure to these bacteria from the environment could be presumed. Clinicians should maintain a high index of suspicion for this treatable disorder. [Copyright &y& Elsevier]

Abstract: In Europe, infant botulism is a rare but probably under-diagnosed disease. With the intent to spread the awareness of this potentially life-threatening disease, we present a review of the literature with the emphasis on European epidemiology and a practical approach to diagnosis. We also report the first two confirmed cases of infant botulism in Slovenia and describe our way to the final diagnosis in a clinical setting where all appropriate diagnostic tests and treatment options are not readily available. The second case is particularly interesting, presenting with profound diarrhea following initial constipation, an unlikely symptom for an infant with botulism and possibly caused by Bacteroides fragilis. [Copyright &y& Elsevier]

Abstract: Nowadays, infant botulism is the most important form of human botulism in some countries. This illness affects infants younger than 52 weeks of age. The infection occurs in the intestinal tract; therefore, ingestion of Clostridium botulinum spores with food is proposed. In some countries, people use chamomile tea as a household remedy for intestinal colics and given this tea to infants. Chamomile can be contaminated with C. botulinum and could be a vehicle of its spores. Our aim was to study the prevalence and spore-load of C. botulinum in chamomile. We analysed 200 samples; the 7.5% of them were contaminated with botulinum spores. However, prevalence of these spores was significantly higher in chamomile sold by weight in herbal stores (unwrapped chamomile) than prevalence in chamomile sold in tea bags (p =0.0055). The spore-load detected in all positive samples was 0.3–0.4 spores per gram of chamomile. We identified C. botulinum types A, B, and F in the 53.3%, 6.7%, and 13.3%, respectively. Chamomile (principally, unwrapped chamomile) is a potencial vehicle of C. botulinum spores, and ingestion of chamomile tea could represent a risk for infant botulism. [Copyright &y& Elsevier]

Previously, we demonstrated that the neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a foodborne botulism-related strain, Okra. In this study, the neurotoxin genes of 111/NT and Okra/NT were amplified and the sequences determined. The nucleotide sequences of the genes for both neurotoxins possessed an open reading frame of 3873 bp that encoded 1291 amino acids. The identities of nucleotide sequences and amino acid sequences were 97.6% and 95.7%, respectively. The ratio of nonsynonymous to synonymous substitutions was 0.47. The amino acid substitutions between 111/NT and Okra/NT occurred mainly in the domain of the C-terminal half of heavy chain (HC) responsible for binding to its receptor complex of protein and ganglioside. To characterize the binding capability of the HC, recombinant genes for the HC and two hybrid HC in which one half of Okra/NT was replaced by the homologous half of 111/NT were constructed and expressed in Escherichia coli. The binding activity of the recombinant HC of 111/NT to the protein receptor synaptotagmin II, in the presence of ganglioside GT1b, was 4.2-fold less than Okra/NT, consistent with the corresponding two NTs. The use of hybrid HC revealed that mutation of 23 residues in carboxy terminal half of HC (1029–1291) of Okra/NT could be attributed to the lower binding activity of 111/NT and thus the differences in binding affinity between the two BoNT/B. [Copyright &y& Elsevier]

Abstract: A total of 48 honey samples were analysed for Clostridium botulinum spores. Samples were prepared by direct addition (DA), dilution centrifugation (DC) and supernatant filtration (SF) methods and cultured in cooked meat medium (CMM) and trypticase peptone glucose yeast (TPGY) enrichment broths were used for the isolation of C. botulinum spores. The DC method was found most efficient while CMM enrichment broth was more successful than TPGY. Six of analysed 48 honey samples were C. botulinum positive (12.5%). Results indicated that honey sold in retail markets of Ankara found to be significantly (12.5%) contaminated with C. botulinum. [Copyright &y& Elsevier]

Abstract: A clinical case of infant botulism was detected in Portugal. This rare occurrence was detected in a child provided from an immigrant family from Eastern Europe. Apart from breast milk, the parents also gave him honey and chamomile tea. Clostridium botulinum type B was identified after bacterial isolation in child faeces, honey and chamomile herbs samples. The Botulism neurotoxin (BoNT) B was detected in the faeces according to CDC Atlanta specific procedures. [Copyright &y& Elsevier]

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 bla CBP 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. [ABSTRACT FROM AUTHOR]

Infant botulism is the intestinal (infectious) toxemia in which swallowed spores of Clostridium botulinum activate in the lumen of the colon and thereby produce botulinum toxin, which after absorption causes flaccid paralysis. Human Botulism Immune Globulin (BIG-IV) neutralizes botulinum toxin types A and B. The US FDA licensed BIG-IV to the California Department of Public Health, its creator and developer, as the public service orphan drug BabyBIG® in October 2003 (N. Engl. J. Med. 2006;354:462–471). International distribution began on a trial basis in July 2005. This report summarizes the 2003–2007 distribution, efficacy and safety data for BIG-IV. In the US, a total of 333 eventually laboratory-confirmed patients residing in 35 states were treated within 1 week of hospital admission: 142 type A, 188 type B, 2 type Ba and 1 type Bf. Mean length of hospital stay was 2.2±1.5 vs. 5.7±5.1 wks for untreated patients in the 1992–97 BIG-IV randomized clinical trial (P<0.001) and did not differ significantly by toxin type of illness. Aggregate hospital stay avoided through use of BIG-IV totaled 22.4 years; aggregate hospital costs avoided totaled at least $28 million (2007 dollars). Four other infant botulism patients (2 type E, 2 type F) were also treated with BIG-IV. Internationally, 10 laboratory-confirmed cases in 4 countries were treated, 4 type A, 5 type B and 1 type Ba. No serious adverse events associated with BIG-IV treatment were reported. In the 4 years since licensure of human BIG-IV (BabyBIG®), its use globally to treat infant botulism patients has demonstrated its continued safety, efficacy and US cost-effectiveness. [Copyright &y& Elsevier]

Abstract: We report a case of infant botulism presenting as primary colonic ileus—mimicking Hirschprung''s megacolon. Infant botulism should be considered in any infant with constipation and neurologic abnormalities. [Copyright &y& Elsevier]

Clostridium botulinum type B has recently been isolated from food-borne and infant botulism cases. The BoNT/B in these cases was divided into two main subtypes, B1 and B2, based on analysis of the amino acid sequences. The genetic properties of the C. botulinum type B strains in relation to infant botulism in Japan (strains 111, Osaka05 and Osaka06) were analyzed by sequencing of the bont/B and nontoxic component genes (ha70, ha17, ha33, p21 and ntnh), PFGE genotyping and southern blot hybridization with bont/B probe. Strain Osaka05 produced particular BoNT/B, which were grouped to a novel variant on phylogenetic analysis. The substitutions of amino acid residues were concentrated in the heavy chain, especially in the HCC subdomain. Strains 111 and Osaka06 were classified as subtype B2. The nontoxic component gene arrangements within these subtypes were identical to each other. Multiplex PCR method for BoNT/B subtyping (B1, B2 and Osaka05) was newly established based on bont/B nucleotide sequences variability. Three isolates from infant botulism in Japan were identified as different genotypes based on Sma I-digested PFGE. The BoNT/B encoding gene was shown to be located on large plasmids (approximately 150 or 260–280kbp) for various subtype strains including isolates from infant botulism in Japan using Southern blot hybridization after nondigested PFGE with bont/B probe. [Copyright &y& Elsevier]