M I N I R E V I E W
`
`Association Between Honey Consumption and
`Infant Botulism
`
`Maria G. Tanzi, Pharm.D., and Michael P. Gabay, Pharm.D.
`
`Infant botulism, a disease that results in a blockade of voluntary motor and
`autonomic functions, was first recognized in the United States in the late
`1970s. Since then, more than 1000 cases in this country have been reported
`to the Centers for Disease Control and Prevention (CDC). Numerous studies
`have shown that the ingestion of honey is linked with infant botulism. In
`addition, honey samples across the United States have tested positive for
`Clostridium botulinum spores and toxins. Such substantial evidence led the
`CDC to recommend that honey not be given to infants younger than 12
`months old. It is important that clinicians be familiar with this risk and
`should not recommend honey-containing products or supplements or the use
`of honey as a flavoring agent for infants in this age group.
`(Pharmacotherapy 2002;22(11):1479–1483)
`
`Honey should not be given to infants younger
`than 12 months old.1–4 This recommendation is
`supported by major pediatric and public health
`organizations, as well as manufacturers of honey
`in the United States. Natural products are
`consumed by approximately 14% of the U.S.
`population.5 However, many parents are unaware
`of the potential danger of honey and administer
`it to their infants. Honey may be a reservoir for
`Clostridium botulinum spores, which have been
`linked to the development of infant botulism.
`Clinicians should become familiar with the risks
`associated with honey and should not
`recommend honey-containing supplements or
`the use of honey as a flavoring agent for children
`less than 12 months old.
`Clostridium botulinum is ubiquitous in the
`environment but is found primarily in soil and
`marine sediment. 3
`It is a gram-positive,
`anaerobic, spore-forming bacterium that
`produces seven distinct neurotoxins, labeled A
`through G. Toxins A, B, and rarely, E, are
`From the Department of Pharmacy Practice, College of
`Pharmacy, University of Illinois, Chicago, Illinois (both
`authors).
`Address reprint requests to Maria G. Tanzi, Pharm.D.,
`Department of Pharmacy Practice, College of Pharmacy,
`University of Illinois, 833 South Wood Street, Chicago, IL
`60612.
`
`responsible for causing disease in humans.1, 2
`Clostridium botulinum spores and toxin are
`carried by dust particles and deposited on fresh
`fruits, vegetables, and other agricultural
`products, including honey. Ingestion of foods
`contaminated with these preformed toxins or
`spores may result in the development of human
`botulism.1, 2 Clostridium botulinum spores are
`dormant forms of the bacteria that can survive
`under harsh conditions, such as elevated
`temperatures (> 100°C), which enables them to
`thrive during food preservation procedures. In
`contrast to the spores, the toxin produced by C.
`botulinum is heat labile and easily destroyed by
`temperatures above 80°C.3 Acidic environments
`also inhibit the growth of C. botulinum and its
`spores.
`Infant botulism occurs after ingestion of C.
`botulinum spores.1–3 These spores germinate
`within the child’s large intestine, multiply rapidly,
`and release neurotoxins responsible for infant
`botulism, primarily A and B. Once absorbed,
`these neurotoxins bind to cholinergic synapses,
`resulting in a blockade of voluntary motor and
`autonomic junctions. Within 18–36 hours of
`ingestion of contaminated food, this blockade
`manifests symptomatically as a symmetric,
`descending, flaccid paralysis of motor and
`
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`Table 1. Documented Cases of Honey Ingestion and Infant Botulism in the United States
`No. of
`No. of Infants with
`Associated
`History of Honey
`Toxins
`Consumption
`3 type A
`3
`3 type B
`Not reported
`47 type A
`34 type B
`25 type A
`16 type B
`33 type A
`35 type B
`
`Positive
`Honey Sample
`1 jar
`
`3 jars
`None analyzed
`
`6 jars
`
`None analyzed
`
`13
`29
`
`12
`
`11
`
`Age of Onset
`5–20 wks6
`
`Not reported7
`3–35 wks8
`
`Not reported9
`
`2–50 wks10
`
`No. of
`Infants
`6
`
`43
`81
`
`41
`
`68
`
`autonomic nerves.1 Constipation is often the
`first symptom in infants with botulism and
`usually precedes the onset of neurologic
`symptoms by a few days. Over time, the infant
`appears lethargic, feeds poorly, and develops a
`weak cry and poor muscle tone. Symptoms
`progress to paralysis of the arms, legs, trunk, and
`respiratory muscles. If left untreated, infant
`botulism can be fatal.1–3
`
`Epidemiology
`Infant botulism was first recognized in the
`United States in 1976. Since then, the frequency
`of the disease has been on the rise, with 1442
`cases reported to the Centers for Disease Control
`and Prevention (CDC) from 1976–1996.4 The
`majority of these cases were from California (~
`50% of all cases), Delaware, Utah, and Hawaii.
`They involved primarily type A and B neuro-
`toxins, which accounted for 46.5% and 51.9% of
`cases, respectively. Approximately 95% of infant
`botulism cases occur in infants less than 6 months
`old; the remaining 5% occur in infants 6–12
`months old. The disease is distributed equally
`between boys and girls and across all major racial
`and ethnic groups. Risk factors for infant
`botulism are poorly understood; however, several
`studies have linked the ingestion of honey to the
`development of infant botulism (Table 1).6–10
`
`Honey Consumption and Infant Botulism in the
`United States
`A prospective study was conducted in 1977 to
`identify any commonalities among the first six
`infants in the United States diagnosed with infant
`botulism.6 Age of onset, type of C. botulinum
`toxin responsible for disease, and food and drugs
`ingested before disease onset were evaluated.
`
`The infants ranged in age from 5–20 weeks old.
`Type A botulinum toxin caused the disease in
`three infants and type B was responsible in the
`other three. Fifteen food and six drug items
`ingested by the infants were tested, including
`mother’s breast milk, honey, rice cereal, oatmeal,
`infant formula, pediatric vitamin preparations,
`pediatric iron supplements, and acetaminophen
`drops. Of these items, only a jar of honey tested
`positive for C. botulinum. This food item had
`been fed to one infant as a honey-and-water
`mixture. Two of the remaining five infants also
`had been fed honey, but no C. botulinum was
`isolated from tested samples.
`From 1976–1978, California reported 43
`documented cases of infant botulism. In 13 of
`these cases, infants had ingested honey before
`disease onset; C. botulinum was isolated from
`three honey samples fed to the affected infants.
`The CDC also reported on the testing of honey
`specimens in California. Approximately 60
`specimens were tested, with 13% testing positive
`for C. botulinum. In 1978, the CDC reported the
`association between honey consumption and
`infant botulism.7 They concluded that honey
`may have been the source of infection in
`approximately one third of the cases reported and
`therefore should be avoided as a food source for
`all infants younger than 12 months old.
`A retrospective analysis of infant botulism
`cases reported to the CDC from January 1, 1975,
`to July 31, 1978, was performed to assess
`epidemiologic characteristics of the disease.8 A
`total of 81 cases were reviewed for similarities.
`Of these cases, 45 (56%) occurred in male infants
`and 36 (44%) occurred in female infants. Type A
`botulinum toxin was responsible for the disease
`in 47 infants and type B in 34 infants. Mean age
`of onset was similar in both groups: 12.5 and
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` 18759114, 2002, 11, Downloaded from https://accpjournals.onlinelibrary.wiley.com/doi/10.1592/phco.22.16.1479.33696 by University Of Texas Libraries, Wiley Online Library on [31/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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`ASSOCIATION BETWEEN HONEY AND INFANT BOTULISM Tanzi and Gabay
`
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`
`10.3 weeks for types A and B, respectively. The
`reported fatality rate was 3.7%. Data on the
`consumption of honey before disease onset were
`available for 59 infants. Twenty-nine (49%) of
`the infants had been fed honey before botulism
`onset. No testing of honey samples was performed.
`A case-control, prospective study was
`performed to assess environmental risk factors
`for infant botulism. 9
`Infant botulism was
`identified through positive fecal specimens of C.
`botulinum or its toxins submitted to the state
`laboratory of California from March 1976–June
`1978. Two or three controls were selected for
`each of the documented cases and matched for
`variables including sex, age, area of residence,
`and hospital of birth. Study investigators
`collected epidemiologic data from the homes of
`infants with documented cases and controls,
`such as food fed to the infant, soil from the yard,
`and household vacuum cleaner dust. If the
`infant had been fed honey and none remained in
`the home, samples of identical brand, size, and
`container were purchased from the family’s
`market. Forty-one children with infant botulism
`were included in the study, with 25 type A
`botulism cases (63 matched controls) and 16
`type B cases (44 matched controls). Forty-three
`percent of the infants with type B botulism had
`been fed honey before the onset of illness
`compared with only 9% of the matched controls
`(p=0.005). No significant difference was found
`between infants with type A botulism and
`controls. In addition, six different honey
`specimens fed to three infants with documented
`cases contained C. botulinum. Ninety honey
`specimens were analyzed, and nine (10%) tested
`positive for C. botulinum. These samples
`contained 5–70 C. botulinum spores/gram of
`honey. Clostridium botulinum spores also were
`identified in three soil samples and dust from one
`vacuum cleaner from the homes of infants with
`documented cases. The authors concluded that
`although C. botulinum is present in the
`environment, honey was an identifiable and
`avoidable source of C. botulinum spores and
`should not be given to infants.
`A prospective, case-control study was
`performed from April 1, 1985, to March 31,
`1987, to determine risk factors for infant
`botulism.10 The authors sought to identify foods
`and environmental factors that may contribute to
`the development of the disease. Sixty-eight
`infants with laboratory-confirmed cases were
`included in the study, and each was matched
`with two control subjects based on date and
`
`hospital of birth. Case patients’ and control
`patients’ families were interviewed by phone to
`obtain the following information: signs of
`disease; infants’ bowel movement patterns;
`location of residence, defined as city, suburban,
`rural, or farm; and type and quantity of food
`exposure before disease onset. Of the 68 infants,
`53% were female, 47% were male, and mean age
`of disease onset was 2 months (range 0.2–11.7
`mo). The most common signs of disease were a
`decrease in bowel movements to less than one
`bowel movement in a 3-day period (69%) and an
`altered cry (25%). Case patients were also more
`likely to have lived in a rural or farm area;
`however, this difference was not significant
`compared with the control group. A significantly
`greater number of infants who tested positive for
`C. botulinum were fed honey before disease onset
`(16% vs 2% of controls, p<0.004). Both type A
`(5 cases) and type B (6 cases) botulism occurred
`in infants who had consumed honey. The
`authors recommended that honey not be fed to
`infants less than 12 months of age because of the
`risk of infant botulism.
`
`Honey Consumption and Infant Botulism
`Outside the United States
`
`In Denmark, a 3-month-old boy was admitted
`to the hospital secondary to poor feeding,
`diminished cry, and motor weakness.11 During
`examination, he was found to have a flaccid facial
`expression and diminished deep tendon reflexes.
`Serum obtained 3 days after admission tested
`positive for C. botulinum, and fecal samples tested
`1 month later were positive for C. sporogenes.
`The parents reported that the infant had been fed
`honey for more than 60 days. The honey
`originated from two sources, one imported and
`one of Danish origin. Only one of the two
`samples of honey was available for testing; it was
`positive for C. sporogenes. No C. botulinum was
`isolated from the honey jar. However, the
`authors noted that C. botulinum was isolated from
`another jar of honey purchased at the same shop
`as the honey fed to the infant.
`An 11-week-old girl was admitted to a hospital
`in Australia after feeding poorly, increased
`lethargy, diminished cry, and decreased bowel
`movements.12 Examination revealed pooled
`secretions, weak gag reflex, diminished muscle
`tone, and decreased spontaneous movements. A
`culture from the stool was positive for C.
`botulinum and its toxins. History from her
`parents revealed that the mother had been
`
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`PHARMACOTHERAPY Volume 22, Number 11, 2002
`
`dipping the infant’s pacifier into a jar of
`commercially available honey. Subsequent
`testing of the honey jar was negative for C.
`botulinum toxin or spores.
`In Italy, a 9-week-old girl was admitted to the
`hospital after 10 days of constipation, diminished
`cry, and lethargy.13 She had general hypotonicity
`and diminished respiratory function. On day 3
`of hospitalization, a fecal sample tested positive
`for C. botulinum type B (200,000 spores/gram of
`stool). The parents reported that they had
`applied honey to sweeten the infant’s pacifier.
`The honey had originated from three sources,
`two retail and one home canned. All three
`samples were available for testing, and the home-
`canned version tested positive for C. botulinum
`type B.
`
`Clostridium botulinum Spores in Infant Foods
`A study in 1978 investigated 55 honey samples
`from 53 commercial lots and 186 samples from
`154 producers to assess the amount of C.
`botulinum spores present in the samples.14 Of the
`241 samples tested, 18 tested positive for C.
`botulinum spores. Two of the commercially
`available honey samples tested positive, one with
`type A and the other with type B. The remaining
`16 positive samples originated from various
`honey producers, and the majority were
`contaminated with type A. The positive samples
`originated from manufacturers in California,
`Florida, Iowa, Michigan, Minnesota, Nebraska,
`Tennessee, and Washington.
`In a study 4 years later, 10 categories of infant
`foods obtained from the Washington, DC, area
`were tested for C. botulinum spores.15
`Infant dry
`cereals, dry formulas, nonfat dry milk,
`pasteurized whole cow’s milk, canned fruits, fruit
`juices, honey, corn syrup, granulated cane sugar,
`and fresh carrots were analyzed. Approximately
`95 samples of each of the 10 items from different
`lots were tested. Two samples of honey tested
`positive for C. botulinum type A. The authors
`concluded that food processing does not include
`steps that are lethal to C. botulinum; therefore, the
`organism may be found in some processed food
`products.
`
`Management of Infant Botulism
`Because minimal treatment options are
`available for infant botulism, management of this
`illness relies heavily on supportive care.
`Monitoring and maintaining respiratory function
`are essential. Approximately 50% of infants
`
`require endotracheal intubation.1 Nutritional
`support with enteral feeding is recommended.1–3
`The only agent available to treat diagnosed infant
`botulism is a human-derived botulism antitoxin,
`also known as botulism-immunoglobulin
`(BIG).1–4 Currently, BIG is obtainable only from
`the California Department of Health Services
`under a treatment investigational new drug
`protocol for types A and B infant botulism.16
`(Physicians may obtain BIG by contacting the
`study office at 510-540-2646, 24 hrs/day.)
`Botulism-immunoglobulin is composed of
`immunoglobulin G (IgG) antibodies and
`antitoxins A and B antibodies in sufficient
`quantities to neutralize circulating levels of
`botulism neurotoxin.17 The infant is given one
`dose of intravenous BIG to help interrupt the
`neuromuscular blockade caused by C. botulinum
`toxin. The recommended total dose is 50 mg/kg
`given as a single intravenous infusion. The
`infusion rate is 25 mg/kg/hour for the first 15
`minutes, then 50 mg/kg/hour thereafter (volume
`not to exceed 75 ml/hr) if no infusion-rate
`reactions occur. Infusion-related reactions
`reported with BIG include flushing, chills, fever,
`back pain, and hypotension. Botulism-
`immunoglobulin should not be given to patients
`with selective immunoglobulin A (IgA)
`deficiency because of the risk of anaphylactic
`reactions secondary to trace amounts of IgA
`present in the product.
`The efficacy of BIG was assessed in a 5-year
`placebo-controlled, randomized trial, which
`showed that infants who received BIG had a
`significant reduction in hospitalizations and
`complications.1–3, 18 Mean intensive care unit and
`hospital stays decreased by more than half, from
`3.5 weeks to 1.5 weeks and from 5.5 weeks to 2.5
`weeks, respectively, in patients treated with BIG
`(p<0.05).18 In addition, patients treated with BIG
`had a significant reduction in ventilator days,
`from 17 to 5 days (p=0.02), and a significant
`reduction in the need for tube feeding, from 10 to
`3.5 weeks (p<0.001). Treatment with BIG
`resulted in substantial cost-savings secondary to
`reduced
`length of hospital stay,
`from
`approximately $128,000 to $59,000 (p<0.001).
`Overall, the prognosis for patients with infant
`botulism is excellent, with a case:fatality ratio of
`less than 1% for infants hospitalized in the
`United States.19
`
`Conclusion
`
`More than 1000 cases of infant botulism have
`
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`ASSOCIATION BETWEEN HONEY AND INFANT BOTULISM Tanzi and Gabay
`
`1483
`
`been reported to the CDC over the past 3
`decades. These numbers are alarming because
`this illness can be fatal if left untreated.
`Numerous case-control studies and case reports
`led to the conclusion that consumption of honey
`by children younger than 12 months old is a
`positive risk factor for the development of infant
`botulism. In addition, analyses of honey
`products showed that approximately 10% of
`samples tested positive for C. botulinum toxin or
`spores. Clinicians should not recommend
`honey-containing supplements or the use of
`honey as a flavoring agent for infants in this age
`group.
`
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` 18759114, 2002, 11, Downloaded from https://accpjournals.onlinelibrary.wiley.com/doi/10.1592/phco.22.16.1479.33696 by University Of Texas Libraries, Wiley Online Library on [31/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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