Case Of Infant Botulism Research Articles

Descriptive Epidemiology of Infant Botulism in California: The First 40 Years

To ascertain the descriptive epidemiology of infant botulism, the flaccid paralysis that results when neurotoxigenic Clostridium species produce botulinum toxin (BoNT) in the infant colon, in its first 40years following initial recognition in California in1976. Cases were defined by laboratory identification of BoNT and/or neurotoxigenic Clostridium species in patients' feces. Parents were interviewed using a structured questionnaire. Descriptive epidemiologic characteristics were compared between 1976-1996 and 1997-2016. From 1976-2016, 1345 cases of infant botulism occurred in 45 of 58 California counties (6.5 cases/100000 live-births/year) caused by BoNT types A, B, Ba, Bf, and F; 88% of cases were ≤6months of age and 51% were female. Cases were white (84.2%), Asian (8.9%), other races (3.8%), and African American (2.8%); 29.4% of cases were Hispanic. More than 99% of cases were hospitalized. Case occurrence peaked in summer-fall. Of 8 designated geographic regions, the Central Coast counties had 3 times the statewide incidence in both 20-year time periods. Breast-fed patients (83%) were more than twice as old at onset as formula-fed patients (median, 4.4 vs 1.7months, respectively; P<.001). BoNT/A cases were older at onset than BoNT/B cases (median, 3.8 vs 2.9months, respectively; P<.001). Comprehensive continuous surveillance of infant botulism for 40years in a large, diversely populated state identified fundamental epidemiologic characteristics of this uncommon illness. Unusual features included greater than 99% case hospitalization, absence of male preponderance, and a distinctive age distribution.

Seven-Year Case-Control Study in California of Risk Factors for Infant Botulism

To ascertain possible risk factors for infant botulism, the intestinal infectious form of human botulism, in the years immediately following its initial recognition in California in1976. Parents of 159 California laboratory-confirmed cases of infant botulism from 1976 to 1983 and 318 healthy controls were interviewed using a comprehensive (>300 factors) questionnaire. "Neighborhood controls" (n=184) were matched on date of birth, sex, race/ethnicity, and neighborhood of residence. "County controls" (n=134) were matched only on date of birth, sex, and county of residence. Age-stratified bivariate and multivariate conditional logistic regression analyses were performed using SAS. All cases required hospitalization. Bivariate analyses identified several risk factors that in multivariate analyses were not significant. In multivariate analyses, risk factors differed with stratification by age. For the ≤2 month-old neighborhood controls comparison, birth order >1, cesarean delivery, ≤1 bowel movements (BMs) per day, and windy residence area were associated with illness hospitalization, and for the county controls comparison, only pacifier use was associated. For the <2 month-old neighborhood controls comparison, <1 bowel movements (BMs) per day, cesarean delivery, birth order >1, and windy residence area were associated with illness hospitalization, and for the county controls comparison, pets in the home was an additional risk factor. With the exception of the ≤2-month-old county controls group, slower intestinal transit time (≤1 BM/d) was associated with illness. Otherwise, our case-control investigation identified few physiologic, environmental, and maternal factors associated with infant botulism hospitalization in California.

Infantile Botulism: One of the Multiple Etiologies of Acute Hypotonia in Infancy

Infant botulism is an uncommon disease with a challenging diagnosis which is often confused with other diseases. This is a report of a case of infant botulism with no history of honey ingestion and responds well to equine immunoglobulin due to the low prevalence and importance of the mentioned disease.

Type F Infant Botulism: Investigation of Recent Clusters and Overview of This Exceedingly Rare Disease.

From 1976 to 2016, neurotoxigenic Clostridium baratii type F caused 18 (<0.5%) reported US infant botulism cases. Six cases occurred during 2012-2013; no common source was identified. Type F infant botulism mostly occurs in very young infants and typically presents more rapidly and severely than illness caused by types A and B botulinum neurotoxin.

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.

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.

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.

Botulism mortality in the USA, 1975-2009.

Botulism had mortality rates >60% before the 1950s. We reviewed confirmed botulism cases in the USA during 1975-2009 including infant, foodborne, wound, and other/unknown acquisition categories, and calculated mortality ratios. We created a multivariate logistic regression model for non-infant cases (foodborne, wound, and other/unknown). Overall mortality was 3.0% with 109 botulism-related deaths among 3,618 botulism cases [18 (<1%) deaths among 2,352 infant botulism cases, 61 (7.1%) deaths among 854 foodborne botulism cases, 18 (5.0%) deaths among 359 wound botulism cases, and 12 (22.6%) deaths among 53 other/unknown botulism cases]. Mortality among all cases increased with age; it was lowest among infants (0.8%) and highest among persons ≥80 years old (34.4%). Toxin type F had higher mortality (13.8%) than types A, B, or E (range, 1.4% to 4.1%). Efforts to reduce botulism mortality should target non-infant transmission categories and older adults.

Complete nucleotide sequence of a plasmid containing the botulinum neurotoxin gene in Clostridium botulinum type B strain 111 isolated from an infant patient in Japan.

Botulinum neurotoxins (BoNTs) are highly potent toxins that are produced by Clostridium botulinum. We determined the complete nucleotide sequence of a plasmid containing the botulinum neurotoxin gene in C. botulinum type B strain 111 in order to obtain an insight into the toxigenicity and evolution of the bont gene in C. botulinum. Group I C. botulinum type B strain 111 was isolated from the first case of infant botulism in Japan in 1995. In previous studies, botulinum neurotoxin subtype B2 (BoNT/B2) produced by strain 111 exhibited different antigenic properties from those of authentic BoNT/B1 produced by strain Okra. We have recently shown that the isolates of strain 111 that lost toxigenicity were cured of the plasmid containing the bont/B2 gene. In the present study, the plasmid (named pCB111) was circular 265,575 bp double-stranded DNA and contained 332 predicted open reading frames (ORFs). 85 gene products of these ORFs could be functionally assigned on the basis of sequence homology to known proteins. The bont/B2 complex genes were located on pCB111 and some gene products may be involved in the conjugative plasmid transfer and horizontal transfer of bont genes. pCB111 was similar to previously identified plasmids containing bont/B1, /B5, or/A3 complex genes in other group I C. botulinum strains. It was suggested that these plasmids had been derived from a common ancestor and had played important roles for the bont gene transfer between C. botulinum.

Infant botulism: First two confirmed cases in Slovenia and literature review

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.

First case of infant botulism in Portugal

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.

Two cases of type A infant botulism in Grenoble, France: no honey for infants

We report two severe cases of infant botulism diagnosed at Grenoble University Hospital, France, respectively in 2006 and 2009. Both cases were characterized by a delay in diagnosis, severe neurological manifestations and extended period of hospitalization in intensive care unit, but a complete recovery. Infant botulism is a rare but life-threatening disease. It primarily affects infants, and the main risk factor is honey ingestion. Diagnosis should be systematically evoked by pediatricians in infants suffering from constipation, fatigue, muscle weakness, difficult feeding and altered cry, but before the onset of generalized flaccid paralysis, so as to administer specific treatment (BabyBIG®, a human derived botulinum antitoxin) at an early stage of the disease when it is most effective. In conclusion, parents should be aware of the role of honey as a source of spores of Clostridium botulinum and therefore infant botulism in the first year of life.

Identification of Novel Linear Megaplasmids Carrying a ß-Lactamase Gene in Neurotoxigenic Clostridium butyricum Type E Strains

Since the first isolation of type E botulinum toxin-producing Clostridium butyricum from two infant botulism cases in Italy in 1984, this peculiar microorganism has been implicated in different forms of botulism worldwide. By applying particular pulsed-field gel electrophoresis run conditions, we were able to show for the first time that ten neurotoxigenic C. butyricum type E strains originated from Italy and China have linear megaplasmids in their genomes. At least four different megaplasmid sizes were identified among the ten neurotoxigenic C. butyricum type E strains. Each isolate displayed a single sized megaplasmid that was shown to possess a linear structure by ATP-dependent exonuclease digestion. Some of the neurotoxigenic C. butyricum type E strains possessed additional smaller circular plasmids. In order to investigate the genetic content of the newly identified megaplasmids, selected gene probes were designed and used in Southern hybridization experiments. Our results revealed that the type E botulinum neurotoxin gene was chromosome-located in all neurotoxigenic C. butyricum type E strains. Similar results were obtained with the 16S rRNA, the tetracycline tet(P) and the lincomycin resistance protein lmrB gene probes. A specific mobA gene probe only hybridized to the smaller plasmids of the Italian C. butyricum type E strains. Of note, a ß-lactamase gene probe hybridized to the megaplasmids of eight neurotoxigenic C. butyricum type E strains, of which seven from clinical sources and the remaining one from a food implicated in foodborne botulism, whereas this ß-lactam antibiotic resistance gene was absent form the megaplasmids of the two soil strains examined. The widespread occurrence among C. butyricum type E strains associated to human disease of linear megaplasmids harboring an antibiotic resistance gene strongly suggests that the megaplasmids could have played an important role in the emergence of C. butyricum type E as a human pathogen.

Universal and specific quantitative detection of botulinum neurotoxin genes

BackgroundClostridium botulinum, an obligate anaerobic spore-forming bacterium, produces seven antigenic variants of botulinum toxin that are distinguished serologically and termed "serotypes". Botulinum toxin blocks the release of acetylcholine at neuromuscular junctions resulting in flaccid paralysis. The potential lethality of the disease warrants a fast and accurate means of diagnosing suspected instances of food contamination or human intoxication. Currently, the Food and Drug Administration (FDA)-accepted assay to detect and type botulinum neurotoxins (BoNTs) is the mouse protection bioassay. While specific and sensitive, this assay requires the use of laboratory animals, may take up to four days to achieve a diagnosis, and is unsuitable for high-throughput analysis. We report here a two-step PCR assay that identifies all toxin types, that achieves the specificity of the mouse bioassay while surpassing it in equivalent sensitivity, that has capability for high-throughput analysis, and that provides quantitative results within hours. The first step of our assay consists of a conventional PCR that detects the presence of C. botulinum regardless of the neurotoxin type. The second step uses quantitative PCR (qPCR) technology to determine the specific serotype of the neurotoxin.ResultsWe assayed purified C. botulinum DNA and crude toxin preparations, as well as food and stool from healthy individuals spiked with purified BoNT DNA, and one stool sample from a case of infant botulism for the presence of the NTNH gene, which is part of the BoNT gene cluster, and for the presence of serotype-specific BoNT genes. The PCR surpassed the mouse bioassay both in specificity and sensitivity, detecting positive signals in BoNT preparations containing well below the 1 LD50 required for detection via the mouse bioassay. These results were type-specific and we were reliably able to quantify as few as 10 genomic copies.ConclusionsWhile other studies have reported conventional or quantitative PCR-based assays for the detection of C. botulinum genes, our procedure's high-throughput capability and its portability allows most laboratories to quickly assess the possible presence of BoNTs either in food processing samples or in suspected cases of botulism. Thus, this assay provides rapid and specific detection of BoNT and toxin complex genes and would enable the targeting of appropriate therapeutics to infected individuals in a timely manner.

Le botulisme infantile en France, 1991–2009

Infant botulism is caused by the ingestion of spores of Clostridium botulinum and affects newborns and infants under 12 months of age. Ingested spores multiply and produce botulinum toxin in the digestive tract, which then induces clinical symptoms. A single French case was described in the literature prior to 1991. We describe the cases of infant botulism identified in France between 1991 and 2009. All clinical suspicions of botulism must be declared in France. Biological confirmation of the disease is provided by the National reference laboratory for anaerobic bacteria and botulism at the Pasteur Institute. During this period, 7 cases of infant botulism were identified, 1 per year from 2004 to 2008 and 2 in 2009. The median age of affected infants was 119 days and all were female. All infants presented with constipation and oculomotor symptoms. All were hospitalized and required mechanical ventilation. The infants recovered from their botulism. The diagnosis of infant botulism was biologically confirmed for all patients. One 4-month-old infant was treated with a single dose of the human-derived botulism antitoxin specific for infant botulism types A and B (BabyBIG®). The infants all had different feeding habits ranging from exclusive breast feeding to a mix of formula feeding and solid food consumption. The consumption of honey, the only documented risk food for this disease, was reported for 3 of the infants. The honey had been placed on the pacifier of 2 infants and directly in the mouth of the 3rd by the mother. Infant botulism, a form of botulism that was previously rarely recognized in France, has been reported more frequently during the last 6 years. This disease remains rare but nonetheless severe. In light of recent epidemiological data, efforts to raise awareness among parents of infants and health professionals on the danger of infant botulism and particularly, its association with honey consumption seems necessary.

Clostridial spores in powdered infant formula

Infant botulism, the intestinal toxemia form of botulism, most commonly follows unavoidable exposure to spores in the environment, such as through contact with dust or soil. During a transient period in infancy, gut flora may not inhibit intestinal outgrowth of ingested clostridial spores. Clostridia then can replicate and produce toxin that is absorbed and causes neuromuscular blockade. Until the practice of avoiding the feeding of honey to infants under 1 year of age, infant botulism in California was highly associated with infants consuming honey that contained clostridial spores. In this issue of The Journal, Barash et al warn that powdered infant formula may pose a risk for infant botulism. Following report of a case of infant botulism in the United Kingdom that was linked to Clostridium botulinum spores recovered from the patient's powdered formula, California investigators sought to identify clostridial organisms in powdered infant formula. Seventeen percent of 30 samples ingested by patients with infant botulism and 78% of 9 market-purchased unopened powdered formula contained clostridial spores; none was C botulinum but the Clostridium species recovered have similar environmental distribution as C botulinum. Contamination of powdered infant formula with Salmonella and Cronobacter (formerly Enterobacter) sakazakii previously has led to infection in infants; the US Food and Drug Administration mandates monitoring for these organisms. The report by Barash et al suggests that a large sampling study of powdered infant formula for neurotoxin-producing Clostridium species should be performed to assess whether formula poses a health risk for infants. Presence of Soil-Dwelling Clostridia in Commercial Powdered Infant FormulasThe Journal of PediatricsVol. 156Issue 3PreviewBecause Clostridium botulinum was isolated from powdered infant formula (PIF) fed to an infant in the United Kingdom who subsequently developed infant botulism and from unopened PIF from the same manufacturer, we tested PIF manufactured in the United States for the presence of clostridial spores. Full-Text PDF

Report of two unlinked cases of infant botulism in the UK in October 2007

Infant botulism is a rare disease in the UK, with the first case being recognized in 1978 and only five subsequent cases being reported before 2007. This study reports two unlinked cases of infant botulism, caused by two distinct strains of Clostridium botulinum (toxin types A and B, respectively), that occurred within a single month in the south-east of England in October 2007. The use of real-time PCR to detect C. botulinum neurotoxin genes in clinical specimens to improve the diagnostic procedure and to follow carriage of the causative organism in the infant gut is described. The laboratory investigation of these two cases demonstrated that a combination of the mouse bioassay, real-time PCR assays and conventional microbiological culture can provide rapid confirmation of a clinical diagnosis and affect patient management. Both infants (aged 4 and 8 months) were previously healthy prior to the onset of symptoms, and in both cases, a diagnosis of infant botulism was delayed for at least 10 days after initial admission to hospital. Once diagnosed, one of the infants was the first in the UK to be treated with human-derived botulism immunoglobulin. Real-time PCR was used to demonstrate that C. botulinum was excreted in the infants' faeces for up to 68 and 81 days, respectively. Despite the infrequency of infant botulism in the UK, clinicians should be aware of this rare but serious condition and should seek microbiological advice when presented with young infants with compatible symptomologies.

Infant Botulism: a network to improve the diagnosis and treatment of a rare and under-diagnosed disease

Infant Botulism is a form of human botulism in which ingested spores of Clostridium botulinum germinate, colonize the infant&rsquo;s colon, in which they produce botulinum neurotoxin. After the toxin is absorbed, binding to peripheral cholinergic synapses occurs, causing flaccid paralysis. The incidence of infant botulism is low, but some underestimation is likely to exist: the disease is difficult to diagnose because its wide spectrum of clinical manifestations which are not pathognomic. Moreover, failure to recognise the disease is probably related to the low index of suspicion: in fact, the experience of clinicians is fundamental in recognising infant botulism. A specific project has been promote to improve knowledge of the disease by training physicians (pediatricians, neurologists, clinical toxicologists) to look out for the possible presence of Infant Botulism cases and improving public awareness through a prevention program. Standardization of therapeutic protocol also by treatment with specific therapeutic measures will be disseminated. A staff of physicians specialized in Clinical Toxicology will be available, 24 hours a day and seven days/week in the Pavia Poison Centre &ndash; National Toxicology Information Center. According to the project, this Centre acts as Reference Center for the clinical diagnosis and the treatment of infant botulism for the correct recognition of typical syndrome, the early diagnosis and the possible therapy with particular attention to antidotic treatment. The National Reference Centre for Botulism at the Istituto Superiore di Sanit&agrave; will offer a 24-hours diagnostic laboratory service to support diagnose in suspected cases of botulism.

Infant Botulism: Two Recent Cases and Literature Review

Infant botulism is a cause for significant pediatric morbidity in the United States, though early recognition and supportive care can greatly improve clinical outcomes. Since the approval of human botulism immune globulin by the United States Food and Drug Administration (FDA) for the treatment of infant botulism in 2003, the importance of prompt initiation of therapy has been emphasized, with clinical suspicion remaining the mainstay of diagnosis. In this report, 2 cases of infant botulism are described. Each presented to the Pediatric Neurology service at our institution in Upstate New York in the spring and summer months of 2007 and were felt to be related to markedly dusty environmental conditions and the probable ingestion of C. botulinum organisms present in soil. Following this, a comprehensive review of the literature regarding infant botulism in the United States is presented, wherein the pathophysiology, clinical features, epidemiology, and treatment are discussed.

Global Occurrence of Infant Botulism, 1976–2006

To summarize the worldwide occurrence of reported infant (intestinal toxemia) botulism cases since first recognition of the disease in 1976. We collected information on infant botulism cases by active and passive surveillance, by provision of therapeutic Human Botulism Immune Globulin to suspected cases, and by searching the medical literature. We defined a case as laboratory-confirmed botulism that occurred in an infant <or=12 months of age that was not caused by the ingestion of botulinum toxin in food. Twenty-six countries representing 5 continents reported the occurrence of at least 1 case of infant botulism among their residents. The United States, Argentina, Australia, Canada, Italy, and Japan, in this order, reported the largest number of cases. A history of honey exposure was significantly more common among case subjects hospitalized outside of the United States than among those who were recently hospitalized in California. Most countries have not yet reported cases of infant botulism. This limited reporting of the disease to date contrasts with the known global occurrence of Clostridium botulinum spores in soils and dust and suggests that infant botulism may be under-recognized, underreported, or both. When bulbar palsies, hypotonia, and weakness are present, physicians should consider the possibility of infant botulism even if the patient has not been fed honey. Publication of additional case reports and surveillance summaries will enhance understanding of the occurrence and extent of this under-recognized disease.