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.     

Infantiler Botulismus

A 7 1/2-month-old male infant presented in hospital with lethargy, reluctance to drink and reduced urinary excretion. The child was diagnosed with infant botulism. We report on the suspected diagnoses and attempts at treatment leading up to the diagnosis of infant botulism. We also describe the further course of the disease after administration of BIG-IV until recovery (9 months later). Using this case as an example, we discuss important findings suspicious of infant botulism, indications for treatment and disease prevention by means of education (infants should not receive honey/maple syrup/corn syrup during their first year).     

Infant botulism: Two case reports and electroneuromyogram findings

Botulism is an uncommon severe neuromuscular disorder. We report two recent cases of confirmed infant botulism diagnosed in an 11-week and a 5-month-old infant along with electroneuromyogram (ENMG) findings. Then, we discuss the EMG features of infant botulism. In severe forms of infant botulism, presence of these features might help decide to use botulinum immune globulin. To our knowledge, case 1 is the first case reported in France based on confirmed dust contamination.     

Infant botulism

We report a case of botulism in a 40 day old infant. The patient presented a descending flaccid paralysis requiring mechanical ventilation for 12 days. She is the first European patient treated with Human Botulism Immune Globulin. A few weeks later a second case of infant botulism was detected in our geographical region in Southern Spain. We emphasise the importance of an early diagnosis and treatment with Human Botulism Immune Globulin to decrease morbidity.     

Is there a link between infant botulism and sudden infant death? Bacteriological results obtained in Central Germany

Despite the fact that botulism was described in Germany for the first time by Kerner in 1820, the disease is almost forgotten in this country. Only about 10-20 cases of classical botulism (intoxication) are recorded every year, including 1-2 cases of clinical infant botulism. As we assumed a high incidence of botulism to be connected with cases of sudden infant death (SID), we undertook the research work presented here. From every case of unexpected infant death up to 12 months of age, standardised specimens (blood, liver and intestine) were taken at autopsy. They were tested for the presence of botulinum neurotoxin (BoNT) and/or bacterial forms of Clostridium botulinum with subsequent BoNT neutralisation tests by the international standard mouse bioassay. Age, sex, pathological findings and season were recorded. Over a 5-year period, 75 samples including 57 SID cases were tested. Free toxin was found in nine and bacterial forms were detected in six samples. Toxin neutralisation revealed the definite presence of BoNT/BoNT producing bacteria (mainly type E), whereas another 11 toxin tests were inconclusive. According to international literature, these 15 cases are to be interpreted as infant botulism. Conclusion: the results show a remarkable incidence of infant botulism without any known previous medical history, partly hidden as sudden infant death. We propose to systematically search for botulism in connection with sudden infant death.     

Electrodiagnosis reliability in the diagnosis of infant botulism.

Infant botulism is confirmed by isolation of Clostridium botulinum from stool culture or by toxin assay. Although electrodiagnosis has been described as a diagnostic tool in infant botulism, our 11-year review of toxin-confirmed cases suggests that electrodiagnosis is not a reliable tool. In the case report presented, results of electrodiagnosis were negative but enema effluent contained adequate concentrations of organism and toxin to confirm the diagnosis.     

Etiologia i epidemiologia botulizmu niemowląt

Foodborne botulism is the most common illness caused by anaerobic, spore-forming bacilli – C. botulinum. Besides classic form of botulism there are less known manifestations of the disease such as wound and infant botulism. Infant botulism is a toxicoinfection occurring in children under one year, usually after ingestion of C. botulinum spores. The prevalence of this disease is extremely rare. However, in recent years there has been an increasing participation of infant botulism in total number of botulism cases with more than half of them being a consequence of honey consumption contaminated with C. botulinum spores. The awareness of the symptoms and hazardous agents of infant botulism is extremely important for the proper diagnosis and successful treatment. There is an increasing evidence that the infant botulism is underestimated and not properly diagnosed thus it may be considered as a sudden infant death syndrome. The European Commission together with World Health Organization and Centres for Disease Control and Prevention gave an opinion on microbiological safety of honey, where they recommend that children under one year of age should not be fed with honey.     

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.     

Infant botulism. Three cases in a small town

Through Dec 31, 1985, there have been six cases of infant botulism reported in Colorado. Three of these infants have lived in the same town of 800 people in western Colorado. Two of these three infants developed infant botulism within a six-month period in late 1981. The infants lived approximately 400 m apart; they had used the same crib at the time each developed botulism. A specimen from the crib yielded Clostridium botulinum, as did four soil samples from the town and house-dust samples from the home of a relative of the second infant. The third infant developed infant botulism in September 1984. This infant had not shared the crib. In this case, all seven samples of soil from various locations in the town yielded C botulinum, as did a sample of house dust from the home of this infant. The occurrence of these three cases in such a small town seems unlikely to be only coincidental. Investigations and reports of other such clusters may provide insight into modes of transmission of infant botulism.     

Infant botulism presenting with poor feeding and lethargy: a review of 4 cases

Infant botulism is a rare cause of hypotonia in young infants. It may present with vague symptoms such as poor feeding and lethargy. We present 4 cases of infant botulism presenting to 2 community hospitals in central Maryland. In each case, poor feeding and lethargy were the chief complaints. One patient was referred to the emergency department with suspected sepsis and one with suspected intussusception. Three patients required endotracheal intubation. All were treated with botulism immune globulin, and all eventually made full recoveries. We discuss the differential diagnosis and provide an overview of infant botulism.     

Epidemiologic study of infant botulism in Pennsylvania: Report of the Infant Botulism Study group

The majority of the almost 400 confirmed cases of infant botulism in the United States have occurred in California, Pennsylvania, and Utah. In Pennsylvania, 44 of 53 (83%) cases occurred within a geographic area of Southeastern Pennsylvania which represents one tenth of the Commonwealth's area and one third of the population at risk for infant botulism. In Southeastern Pennsylvania, a map of the residences of cases circumscribes a discrete ring around Philadelphia. A case-control study performed to seek host-related risk factors, identifies the significant associations of botulism with infants who are white, breast-fed, and born at term into two-parent families with hospitalization insurance. County control studies were performed to identify differences in host-related factors between areas of high and low prevalence of botulism. Although some "protection" could be afforded Philadelphia infants by their feeding and family characteristics, the differences in case rates between Philadelphia and the botulism "ring counties" cannot be explained entirely by host-related factors. Further, the absence of botulism in counties just outside of the botulism "ring," where infants were found to have identical potential risk factors, suggests that an uneven distribution of botulinal spores in the environment is the most significant determinant of case rate.     

Honey and other environmental risk factors for infant botulism.

Infant botulism results from the in vivo production of toxin by Clostridium botulinum after it has colonized the infant's gut. Epidemiologic and laboratory investigations of this recently recognized disease were undertaken to identify risk factors and routes by which C. botulinum spores might reach susceptible infants. Clostridium botulinum organisms, but no preformed toxin, were identified in six different honey specimens fed to three California patients with infant botulism, as well as from 10% (9/90) of honey specimens studied. By food exposure history, honey was significantly associated with type B infant botulism (P = 0.005). In California, 29.2% (12/41) of hospitalized patients had been fed honey prior to onset of constipation; worldwide, honey exposure occurred in 34.7% (28/75) of hospitalized cases. Of all food items tested, only honey contained C. botulinum organisms. On household vacuum cleaner dust specimens and five soil specimens (three from case homes, two from control homes) contained Clostridium botulinum. The known ubiquitous distribution of C. botulinum implies that exposure to its spores is universal and that host factors contribute importantly to the pathogenesis of infant botulism. However, honey is now an identified and avoidable source of C. botulinum spores, and it therefore should not be fed to infants.     

Infant botulism in Australia — a case report

ABSTRACT. The syndrome of infant botulism was first recognised in late 1975 and the majority of cases reported have been from the United States of America. One case has been reported from the United Kingdom and one from Canada.
A three-month-old male infant from Victoria, Australia presented with constipation, marked hypotonia, limb weakness, ptosis, facial weakness and inability to suck and swallow. These abnormalities resolved and he returned to normal over the ensuing months.
A diagnosis of infant botulism was confirmed after the isolation of Clostridium botulinum type B from the faeces.
Infant botulism has now been recognised in four different countries and it is likely than with increasing awareness of this striking clinical syndrome, more cases will be identified.     

The first case of type B infant botulism in Japan

A six-month-old girl with a 5 consecutive day history of constipation and poor feeding developed generalized weakness, poor head control, difficulties in sucking and swallowing, and cranial nerve dysfunction within a few days. These characteristic manifestations and clinical course prompted examination of the possibility of infant botulism, although no history of eating honey was obtained. Mouse bioassay performed with enema effluent demonstrated type B botulinum toxin. Culture of the effluent was positive for Clostridium botulinum type B. This is the first case of type B infant botulism in Japan.     

Risk factors for infant botulism in the United States

To define risk factors for infant botulism, we performed a 2-year prospective case-control study of 68 laboratory-confirmed cases in infants living in the United States, outside of California. For each case patient, two control subjects were matched by date and hospital of birth or county birth records. By univariate analysis, breast-feeding (odds ratio = 2.9) and consumption of honey (odds ratio = 9.8) were associated with disease, but only 11 case patients (16%) had eaten honey. Decreased frequency of bowel movement (less than one per day for at least 2 months) was also associated with disease in infants 2 months of age and older (odds ratio = 5.2). Risk factors changed with the age of the patient at disease onset when analyzed by multivariate logistic regression methods. For infants less than 2 months old, living in a rural area or on a farm was the only significant risk factor (odds ratio = 6.4). For infants 2 months of age and older, breast-feeding (odds ratio = 3.8), less than one bowel movement per day for at least 2 months (odds ratio = 2.9), and ingestion of corn syrup (odds ratio = 5.2) were associated with disease. The severity of the disease was similar for breast- and bottle-fed infants. Clearly defined food exposures account for a minority of infant botulism cases. Preexisting host factors, such as intestinal flora and frequency of bowel movements, may be the most important risk factors for development of disease.     

Clinical mimics of infant botulism

Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992-1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998-2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The approximately 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation.     

Catastrophic presentation of infant botulism may obscure or delay diagnosis

Three infants with infant botulism are presented to illustrate how atypical, early, and severe features may obscure or delay diagnosis. Two boys aged 6 weeks and 20 days, respectively, presented with rapid deterioration after brief periods of poor feeding, one with an apparent life-threatening event at home and the other with a full cardiopulmonary arrest. Initial abnormal laboratory findings of coagulopathy suggested sepsis in the first infant. In the second infant, severe acidosis and hypoglycemia suggested an underlying metabolic disorder. A third infant, aged 1 month, was hospitalized originally with an admitting diagnosis of "pharyngitis" resulting from his inability to take adequate feedings. He received intravenous fluids and antibiotics. One week later he suffered a respiratory arrest. Laboratory findings of severe hyponatremia and acidosis at the time of his arrest suggested a metabolic etiology. Even retrospectively, none of these infants had the typical initial complaint of constipation, and none were noted to have ptosis or facial weakness before catastrophic collapse. However, in each case, the parent had initially brought the child to the physician for "poor feeding" or "poor suck," which was not recognized by medical personnel as a result of bulbar weakness. Ultimately, all 3 infants were found to have infant botulism. All 3 had received antibiotics before catastrophic collapse, possibly contributing to the rapidity of the deterioration. Each recovered, although the delay in diagnosis made them ineligible for treatment with botulism immunoglobulin.     

Infant botulism and sudden infant death syndrome

Infant botulism represents a distinct entity of botulism. Ingestion of the ubiquitously present spores of Clostridium botulinum leads to germination of the organism and neurotoxin production in the infant intestine. Symptoms typically develop gradually in contrast to classical food botulism in which an acute onset of symptoms shortly after the ingestion of preformed toxin in a food is characteristic. Microbiologically, the diagnosis is established by identification of Clostridium botulinum organism and toxin in stool specimen. However, positive results in these tests provide only indirect evidence for the clinical relevance of the neurotoxin since asymptomatic carriers have been found. The toxin irreversibly blocks the release of acetylcholin from the motoric end plate which results in muscle weakness and paralysis. Depending on the amount of toxin produced, infant botulism exhibits a broad clinical spectrum ranging from oligosymptomatic forms to a fulminant course with acute respiratory failure within hours leading to sudden death. Unrecognized mild forms or beginning muscle weakness can be a co-factor for other risk factors of sudden infant death (SIDS). In studies analyzing infants who died from SIDS, botulism bacteria or toxin were found in up to 20 % of cases. Infant botulism therefore represents an important differential diagnosis of unexplained and inconclusive muscular hypotonia in the first year of life.     

Antidiuretic hormone excess in infant botulism

Two infants developed evidence of antidiuretic hormone excess as a complication of infant botulism. Neither child received mechanical ventilatory support before the development of hyponatremia, serum hyposmolality, and urinary hyperosmolality. Both infants responded to fluid-intake restriction. The appearance of hyponatremia in an infant with botulism should suggest antidiuretic hormone excess. The recognition of this entity will lead to its appropriate management with fluid-intake restriction.     

Of war and sausages: A case‐directed review of infant botulism

Within a 3‐month period, two infants presented non‐specifically to hospital and rapidly progressed developing flaccid paralysis. Both children were diagnosed with infant botulism. We briefly review these two cases and discuss the diagnostic and management issues involved with this rare childhood disease.