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Published Ahead of Print 14 September 2011.
10.1128/CVI.05261-11. 2011, 18(11):1845. DOI:Clin. Vaccine. Immunol.
and Laura I. T. de Jong
Bianco, Omar J. Sartori, María L. Piovano, Carolina Lúquez
Elida E. Vanella de Cuetos, Rafael A. Fernandez, María I.
Treatment of Infant Botulism
Equine Botulinum Antitoxin for the
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CLINICAL AND VACCINE IMMUNOLOGY, Nov. 2011, p. 1845–1849 Vol. 18, No. 11
1556-6811/11/$12.00 doi:10.1128/CVI.05261-11
Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Equine Botulinum Antitoxin for the Treatment of Infant Botulism
䌤
Elida E. Vanella de Cuetos,
1
†* Rafael A. Fernandez,
2
† María I. Bianco,
2
†§ Omar J. Sartori,
3
María L. Piovano,
1
Carolina Lu´quez,
2
‡ and Laura I. T. de Jong
2
Unidad de Terapia Intensiva, Hospital Pedia´trico Humberto J. Notti, Mendoza, Argentina
1
; Area Microbiología, Facultad de
Ciencias Me´dicas, Universidad Nacional de Cuyo, Mendoza, Argentina
2
; and Area de Epidemiología,
Hospital Pedia´trico Humberto J. Notti, Mendoza, Argentina
3
Received 27 June 2011/Returned for modification 8 August 2011/Accepted 1 September 2011
Infant botulism is the most common form of human botulism in Argentina and the United States. BabyBIG
(botulism immune globulin intravenous [human]) is the antitoxin of choice for specific treatment of infant
botulism in the United States. However, its high cost limits its use in many countries. We report here the
effectiveness and safety of equine botulinum antitoxin (EqBA) as an alternative treatment. We conducted an
analytical, observational, retrospective, and longitudinal study on cases of infant botulism registered in
Mendoza, Argentina, from 1993 to 2007. We analyzed 92 medical records of laboratory-confirmed cases and
evaluated the safety and efficacy of treatment with EqBA. Forty-nine laboratory-confirmed cases of infant
botulism demanding admission in intensive care units and mechanical ventilation included 31 treated with
EqBA within the 5 days after the onset of signs and 18 untreated with EqBA. EqBA-treated patients had a
reduction in the mean length of hospital stay of 23.9 days (Pⴝ0.0007). For infants treated with EqBA, the
intensive care unit stay was shortened by 11.2 days (Pⴝ0.0036), mechanical ventilation was reduced by
11.1 days (Pⴝ0.0155), and tube feeding was reduced by 24.4 days (Pⴝ0.0001). The incidence of sepsis
in EqBA-treated patients was 47.3% lower (Pⴝ0.0017) than in the untreated ones. Neither sequelae nor
adverse effects attributable to EqBA were noticed, except for one infant who developed a transient
erythematous rash. These results suggest that prompt treatment of infant botulism with EqBA is safe and
effective and that EqBA could be considered an alternative specific treatment for infant botulism when
BabyBIG is not available.
Infant botulism is an intestinal toxemia that affects infants
younger than 1 year, and it occurs usually between 2 and 24
weeks of age (3). Infant botulism should be strongly suspected
in any infant who presents constipation (more than 3 days
without defecation), sluggish or fixed pupils, and any sign of
muscle hypotonia (20, 21). Infant botulism occurs when swal-
lowed botulinum spores germinate, and then vegetative cells
multiply, temporally colonize the large intestine, and synthe-
size botulinum neurotoxin (BoNT) in situ. The neurotoxin is
absorbed and carried out by the bloodstream to neuromuscular
junctions, where it blocks the release of acetylcholine, causing
a flaccid paralysis. Infant botulism presents a broad spectrum
of severity ranging from mild muscle hypotonia, manageable
on an outpatient basis, to sudden death caused by respiratory
arrest (3). The clinical course of infant botulism tends to be
slowly progressive and is followed by a long recovery period.
Return of autonomic function may be slower than neuromus-
cular function. The clinical picture can vary greatly depending
on the severity of infection (15).
Clostridium botulinum is the main causal agent of this tox-
emia, but some rare neurotoxigenic strains of Clostridium bu-
tyricum and Clostridium baratii have been implicated in cases of
infant botulism (1, 7, 8, 16, 26). Clostridia spores are present in
soil, their main reservoir, and they can be transported in dust
particles and dispersed by the wind, exposing people repeat-
edly to botulism spores. Environmental exposure has been
identified as an important risk factor for infant botulism (13,
21, 22, 30), especially in arid regions (14, 24). Honey consump-
tion has also been identified as a risk factor for infant botulism
(5, 15, 18, 27) although it may account for at most 20% of the
cases (29). Moreover, in Argentina, botulinum spores have
been detected in medicinal plants commonly given to infants as
household remedies (9, 10, 28).
A case of infant botulism is defined as laboratory-confirmed
botulism occurring at 12 months of age or less (without inges-
tion of BoNT already present in food), where patients present
a characteristic flaccid paralysis and BoNT in serum and/or
where BoNT-producing clostridia are identified in a patient’s
feces or enema specimen. As of 2006, 26 countries had re-
ported the occurrence of at least one case of infant botulism
among their inhabitants, and the largest numbers of cases have
been reported, in descending order, by the United States, Ar-
gentina, Australia, Canada, Italy, and Japan (19). Remarkably,
most countries have not reported infant botulism cases yet.
This limited reporting of infant botulism contrasts with the
known global occurrence of C. botulinum spores in soils and
dust, and it suggests that infant botulism could be underrec-
ognized, underreported, or both (20). At present, infant bot-
ulism is the most common form of human botulism in Argen-
* Corresponding author. Mailing address: Unidad de Cuidados In-
tensivos, Hospital Pedia´trico Humberto J. Notti, Suipacha 1479, CP
M5501AWA, Godoy Cruz, Mendoza, Argentina. Phone: 54 261
4132649. Fax: 54 261 4494047. E-mail: elicuetos@yahoo.com.ar.
§ Present address: Laboratory of Bacterial Genetics, Fundacio´n In-
stituto Leloir, Ciudad Auto´noma de Buenos Aires, Buenos Aires,
Argentina.
‡ Present address: Enteric Diseases Laboratory Branch, Centers for
Disease Control and Prevention, Atlanta, GA.
† These authors contributed equally to this work.
䌤
Published ahead of print on 14 September 2011.
1845
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tina (25) and in the United States (12). From 1982 to 2010,
Argentina reported 605 laboratory-confirmed cases of infant
botulism, with a mean of 39.5 cases per year in the last 10
years (M. I. Farace, Administracio´n Nacional de Laborato-
rios e Institutos de Salud Dr. Carlos G. Malbra´n, and R. A.
Ferna´ndez, A
´rea Microbiología, Facultad de Ciencias Me´di-
cas, Universidad Nacional de Cuyo, unpublished data). The
average annual incidence of infant botulism in Argentina is
similar to that of the United States: 2.2 per 100,000 live
births in Argentina (25) and 1.9 per 100,000 live births in the
United States (12).
All cases of infant botulism registered in Argentina have
been caused by BoNT type A, except one case caused by type
B (9). In the United States, BoNT types A and B have been
implicated in almost all cases of infant botulism (19).
Specific treatment of infant botulism consists in the admin-
istration of botulinum antitoxin. In the United States, the Cal-
ifornia Department of Public Health developed a human-de-
rived botulism antitoxin (BabyBIG) exclusively for treatment
of infant botulism (4, 6). BabyBIG is safe and effective for
infant botulism type A and type B, and it was shown to be
cost-effective by U.S. standards (23). However, its high cost
($45,300 per vial) (23) may not be affordable for people or
health systems of many countries, including Argentina. Com-
mercial equine botulinum antitoxin (EqBA) has been available
in the United States since 1940 (4), but it has rarely been used
in infant botulism cases because of the risk of inducing lifelong
hypersensitivity to equine antigens, its short half-life (5 to 8
days), and lack of evidence of its benefit (12, 15). While up to
9% of patients might develop hypersensitivity to equine sera,
severe reactions are rare (23). In this study, we report the
effectiveness and safety of the EqBA as treatment for infant
botulism.
MATERIALS AND METHODS
Study design. This is an analytical, observational, retrospective, and longitu-
dinal study.
Patients and eligibility. We reviewed medical records of infant botulism cases
that occurred in Mendoza, Argentina, from January 1993 to December 2007.
Data regarding clinical features, laboratory diagnosis, and treatment were ex-
tracted from each medical record.
We considered the following inclusion criteria: (i) laboratory confirmation of
botulism, (ii) requirement of intensive care and mechanical ventilation, and (iii)
treatment with EqBA within 5 days from the onset of signs (for patients who
received EqBA). This enrollment limitation was decided based on the concern
that any efficacy of EqBA could decrease over time as motor-nerve intoxication
continues (6).
Clinical diagnosis was confirmed by detection of BoNT in stool or serum.
Identification of C. botulinum in stool samples supported the diagnosis. Fecal and
enema samples were tested by established methods to identify BoNT and BoNT-
producing clostridia (17, 25). Laboratory diagnosis was carried out in A
´rea Micro-
biología, Facultad de Ciencias Me´dicas, Universidad Nacional de Cuyo.
Study groups. In this retrospective study, medical records were reviewed in
order to classify patients into two groups: (i) EqBA-treated patients, comprised
of infants who received treatment with EqBA, and (ii) untreated patients, com-
prised of infants who did not receive antitoxin treatment (Fig. 1). Supporting
treatment at the intensive care unit was the same for both groups: all patients
received tube or intravenous feeding, upper airway clearing, mechanical venti-
lation, physical therapy, and enemas for clearing out the bowel, as needed. Vital
functions were monitored in all cases.
Outcome measures. We evaluated the following variables: age, length of hos-
pital stay, length of stay in the intensive care unit, number of days on mechanical
ventilation, and number of days on tube feeding. The primary safety of EqBA
was evaluated by the occurrence of adverse effects, including possible allergic
reactions. The primary efficacy was determined by length of the hospital stay.
Secondary efficacy was evaluated by duration of stay in the intensive care unit,
number of days on mechanical ventilation, and number of days on tube feeding.
Additionally, we analyzed secondary complications: digestive, neurological, and
cardiovascular infections (sepsis); pneumonia (associated with mechanical ven-
tilation or caused by aspiration); immunological complications; and sequelae.
Description of EqBA and its administration. The following was extracted
from the clinical records. Specific treatment was conditioned by the availabil-
ity of EqBA, which was supplied by the Public Department of Health. Each
FIG. 1. Enrollment, follow-up, and data analysis in the retrospective study. A total of 92 laboratory-confirmed cases of infant botulism
diagnosed in Mendoza, Argentina (1993 to 2007), were evaluated for eligibility. Forty-nine patients were enrolled in the study; the rest of the
patients were excluded because they were admitted to a normal pediatric room, did not receive mechanical ventilation, were diagnosed 7 days after
onset the symptoms, and/or received EqBA 7 days after the onset of symptoms. ICU, intensive care unit.
1846 VANELLA DE CUETOS ET AL. CLIN.VACCINE IMMUNOL.
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vial of EqBA contained 7,500 IU of type A and 5,500 IU of type B. The
antitoxin was administered as a single intravenous slow infusion (4 to 6 h) of
500 IU (type A) per kilogram of body weight, diluted in 0.9% saline at a 1:10
dilution.
Before administration of EqBA, patients were subjected to a test of sensitivity,
which consisted of an intradermal injection of 0.1 ml of EqBA at a dilution of
1:1,000 (in distilled water). Three patients presented sensitivity-positive test
results and were subjected to desensitization. This procedure was carried out by
serial subcutaneous injections of antitoxin at intervals of 20 min (Table 1). In all
cases, the EqBA used was a bivalent botulism antitoxin (AB) produced by
Aventis Pasteur. It is a licensed product supplied in single-dose vials and consists
of a refined and concentrated liquid preparation of horse (equine) globulins
modified by enzymatic digestion. Each vial contains the following: 7,500 IU
(equivalent to 2,381 U.S. units) of type A and 5,500 IU (equivalent to 1,839 U.S.
units) of type B.
Statistical analysis. Analysis of data was performed with standard statistical
software (Statistix, version 7.0; Analytical Software, Tallahassee, FL). Differ-
ences between treated and untreated patients (quantitative continuous variables)
were examined with a Mann-Whitney test with a significance level of 0.05.
Proportions were analyzed by Fisher’s exact test.
RESULTS
Between January 1993 and December 2007, 92 infant botu-
lism cases were registered in Mendoza, Argentina. All of them
were caused by C. botulinum type A. The lethality in this
period was 5.4% (5/92). The laboratory diagnosis of the five
patients who died was confirmed after a week of the onset of
symptoms. According to the inclusion criteria, patients admit-
ted to a normal pediatric room, patients that did not need
mechanical ventilation, and patients treated with EqBA after 5
days from the onset of symptoms were excluded. Forty-nine
out of the 92 laboratory-confirmed cases met the inclusion
criteria. All patients received supportive treatment, which con-
sisted of mechanical ventilation, tube or intravenous feeding,
upper airway hygiene, physical therapy, monitoring of vital
functions, and enema, if necessary. Thirty-one patients were
treated with EqBA, and 18 were not treated with antitoxin
(Fig. 1). The baseline characteristics of the two groups were
similar. Laboratory diagnosis of the 49 patients was confirmed
within 24 to 48 h after the arrival of the sample to the labora-
tory. The rapid laboratory diagnosis was essential because only
patients with confirmed infant botulism received specific treat-
ment with EqBA.
The mean length of the hospital stay of EqBA-treated in-
fants was 23.9 days shorter than that in patients who did not
receive EqBA (P⫽0.0007) (Table 2). The secondary outcome
measures were also significantly shorter in the EqBA-treated
group: duration in intensive care was shortened by 11.2 days
(P⫽0.0036), duration on mechanical ventilation was short-
ened by 11.1 days (P⫽0.0155), and duration on tube or
intravenous feeding was shortened by 24.4 days (P⫽0.0001)
(Table 2). Regarding complications, the incidence of sepsis in
EqBA-treated infants was 47.3% lower (P⫽0.0017) than in
untreated patients (Table 2). Severe residual hypotonia was
noticed in four untreated infants while none of the EqBA-
treated patients presented this sequela (Table 2). Hypotonic
patients recovered by 90 days after discharge from the hospital.
No adverse reactions attributable to administration of EqBA
were noticed, except for one infant treated with EqBA who
developed a transient erythematous skin rash.
In both groups, EqBA-treated and untreated patients, phy-
sicians followed the standardized criteria for hospital dis-
charge: no further need for inpatient care, no need for me-
chanical ventilation for at least 3 days, no worsening of
paralysis in the previous 3 days and a demonstrated improve-
ment in motor and bulbar function, and 3 days of intake by
TABLE 1. Desensitization to EqBA by subcutaneous route
Dose no.
a
Dilution in normal saline Vol (ml)
1 1:20 0.05
2 1:10 0.10
3 1:10 0.30
4 Undiluted 0.10
5 Undiluted 0.20
6 Undiluted 0.50
a
Each dose was administered consistently at 20-min intervals.
TABLE 2. Results of safety and primary and secondary efficacy in 49 patients with infant botulism
Parameter Value for the group
Pvalue
Untreated EqBA-treated
No. of patients 18 31
Age (mos.) at admission (mean ⫾SEM 关range兴) 4.0 ⫾0.5 (1–7) 3.5 ⫾0.3 (1–7) NS
b
Outcome variable (mean ⫾SEM 关range兴)
Length of hospital stay (days) 52.6 ⫾6.8 (19–130) 28.7 ⫾2.1 (12–60) 0.0007
Length of ICU stay (days)
a
28.3 ⫾4.3 (8–89) 17.1 ⫾0.9 (8–30) 0.0036
Duration of mechanical ventilation (days) 25.4 ⫾4.5 (7–88) 14.3 ⫾0.9 (7–29) 0.0155
Duration of tube or intravenous feeding (days) 49.2 ⫾6.1 (19–120) 24.8 ⫾1.8 (12–50) 0.0001
Incidence of complication (no. of positive patients/total no. of patients 关%兴)
Bacteremia (sepsis) 12/18 (66.7%) 6/31 (19.4%) 0.0017
Pneumonia at admission 14/18 (77.8%) 20/31 (64.5%) NS
Pneumonia during mechanical ventilation 18/18 (100%) 19/31 (61.3%) 0.0018
Incidence of sequelae (no. of positive patients/total no. of patients 关%兴)
Severe hypotonia 4/18 (22.2%) 0/31 (0%) 0.0144
Laryngeal stenosis 1/18 (5.6%) 0/31 (0%) NS
a
ICU, intensive care unit.
b
NS, not significant.
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tube feeding of 25% or less of maintenance volume and calo-
ries, with the remainder consumed by mouth.
DISCUSSION
Infant botulism is a severe neurological disease that fre-
quently requires hospitalization in intensive care units and
mechanical ventilation. Infant botulism is considered an or-
phan disease, and there was no adequate specific treatment
available until the approval of BabyBIG by the Food and
Drugs Administration (FDA), in October 2003 (4, 6, 11). Ar-
non and colleagues demonstrated that treatment of infant bot-
ulism with BabyBIG is safe and effective, reducing the severity
and duration of the illness as well as the hospital cost (6).
However, many countries, including Argentina, cannot afford
the cost of the BabyBIG. For these reasons, the use of EqBA
could be an alternative specific treatment for infant botulism
when BabyBIG is not available.
Early administration of EqBA to adult patients with food-
borne and wound botulism was associated with improved out-
comes in retrospective and observational studies. Approxi-
mately 6% of adults with food-borne botulism had anaphylaxis
or serum sickness when treated with one or two vials of EqBA
(6). In the United States, few patients with infant botulism
have been treated with EqBA because of its potential for
lifelong sensitization to equine proteins and the possibility that
anaphylactic reactions to the EqBA might be more severe in
infants. However, the efficacy of EqBA for infant botulism
treatment has never been evaluated in a controlled trial (12).
Recently, in the United States, a patient with infant botulism
caused by C. baratii, which produces neurotoxin type F, was
treated with heptavalent EqBA (2). No adverse effect to the
EqBA was reported in this patient.
In this study, we observed that prompt treatment with EqBA
within 5 days from the onset of symptoms decreased the se-
verity of the illness and the mean hospital stay. Infants that
received EqBA showed a significantly shorter stay in intensive
care, on mechanical ventilation, and on tube or intravenous
feeding than patients who did not receive this specific treat-
ment. Moreover, treatment with EqBA showed no serious
adverse effects, and only one patient presented a transient,
blush-like erythematous rash. However, it is important to note
that a few patients treated with BabyBIG experienced a tran-
sient, blush-like erythematous rash, perhaps related to anti-
toxin (6).
Specific treatment of infant botulism should be initiated
as soon as possible. For the cases reported here, early clinical
suspicion and confirmation by the laboratory made possible the
specific treatment within 5 days of the beginning of the symptoms.
In the 49 cases of infant botulism analyzed, the laboratory diag-
nosis was obtained within 24 to 48 h after the arrival of the
samples. This was possible because our laboratory is near the
hospitals and is available every day of the year.
Even though the number of cases reported in this study is
small, the results suggest that EqBA deserves careful consid-
eration as an alternative specific treatment for infant botulism
when BabyBIG is not available. A definitive statement on the
role of EqBA in the treatment of infant botulism should be
reached by a prospective double-blinded randomized trial
comparing EqBA with placebo or even BabyBIG. A despeci-
ated equine immune globulin with lower antigenicity also de-
serves serious consideration.
ACKNOWLEDGMENTS
We thank Fernando D. Saraví for the review of the earlier draft of
this paper and Elcira Maneschi for assisting with the statistical analysis.
This work was supported by grants from Facultad de Ciencias Me´di-
cas and Secretaría de Ciencia y Te´cnica, Universidad Nacional de
Cuyo, Mendoza, Argentina. M.I. Bianco had fellowship assistance
from CONICET, Argentina.
REFERENCES
1. Abe, Y., T. Negasawa, C. A. Monma, and Oka. 2008. Infantile botulism
caused by Clostridium butyricum type E toxin. Pediatr. Neurol. 38:55–57.
2. Al-Sayyed, B. 2009. A 3-day-old boy with acute flaccid paralysis. Pediatr.
Ann. 38:479–482.
3. Arnon, S. S. 2004. Infant botulism, p. 1758–1766. In R. D. Feigen, J. D.
Cherry, G. J. Demmler, S. L. Kaplan, W. B. Saunders (ed.), Textbook of
pediatric infectious disease, 5th ed. Lippincott, Williams & Wilkins, Phila-
delphia, PA.
4. Arnon, S. S. 2007. Creation and development of the public service orphan
drug human botulism immune globulin. Pediatrics 119:785–789.
5. Arnon, S. S., et al. 1979. Honey and other environmental risk factors for
infant botulism. J. Pediatr. 94:331–336.
6. Arnon, S. S., R. Schechter, S. E. Maslanka, N. P. Jewell, and C. L. Hatheway.
2006. Human botulism immune globulin for the treatment of infant botulism.
N. Engl. J. Med. 354:462–471.
7. Aureli, P., et al. 1986. Two cases of type E infant botulism caused by
neurotoxigenic Clostridium butyricum in Italy. J. Infect. Dis. 154:207–211.
8. Barash, J. R., T. W. H. Tang, and S. S. Arnon. 2005. First case of infant
botulism caused by Clostridium baratii type F in California. J. Clin. Micro-
biol. 43:4280–4282.
9. Bianco, M. I., C. Lu´quez, L. I. T. de Jong, and R. A. Ferna´ndez. 2008.
Presence of Clostridium botulinum spores in Matricaria chamomilla (cham-
omile) and its relationship with infant botulism. Int. J. Food. Microbiol.
121:357–360.
10. Bianco, M. I., C. Lu´quez, L. I. T. De Jong, and R. A. Ferna´ndez. 2009. Linden
flower (Tilia spp.) as potential vehicle of Clostridium botulinum spores in the
transmission of infant botulism. Rev. Arg. Microbiol. 41:232–236.
11. California Department of Public Health. 10 March 2009, accession date.
BabyBIG, botulism immune globulin intravenous (human) (BIG-IV).
California Department of Public Health, Richmond, CA.http://www
.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts
/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts
/UCM117160.pdf.
12. Centers for Disease Control and Prevention. 1998. Botulism in the United
States 1899–1996: handbook for epidemiologists, clinicians, and laboratory
workers. Centers for Disease Control and Prevention, Atlanta, GA.
13. Chin, J., S. S. Arnon, and T. F. Midura. 1979. Food and environmental
aspects of infant botulism in California. Rev. Infect. Dis. 1:693–696.
14. de Jong, L. I. T., R. A. Ferna´ndez, M. I. Bianco, C. Lu´quez, and A. S.
Ciccarelli. 2003. Transmisio´n del botulismo del lactante. Prensa Med. Arg.
90:188–194.
15. Fox, C. K., C. A. Keet, and J. B. Strober. 2005. Recent advances in infant
botulism. Pediatr. Neurol. 32:149–154.
16. Hall, J. D., L. M. McCroskey, B. J. Pincomb, and C. L. Hatheway. 1985.
Isolation of an organism resembling Clostridium baratii which produces type
F botulinal toxin from an infant with botulism. J. Clin. Microbiol. 21:654–
655.
17. Hatheway, C. L., and L. M. McCroskey. 1987. Examination of feces and
serum for diagnosis of infant botulism in 336 patients. J. Clin. Microbiol.
25:2334–2338.
18. Hauschild, A. H. W., R. Hilsheimer, K. F. Weiss, and R. B. Burke. 1988.
Clostridium botulinum in honey, syrups, and dry infant cereals. J. Food. Prot.
51:892–894.
19. Koepke, R., J. Sobel, and S. S. Arnon. 2008. Global occurrence of infant
botulism, 1976–2006. Pediatrics 122:e73–e82.
20. Lentini, E., R. A. Ferna´ndez, and G. N. Arenas. 1986. Botulismo del lactante.
Arch. Arg. Pediatr. 84:351–354.
21. Lentini, E., R. A. Ferna´ndez, A. S. Ciccarelli, and D. F. Gime´nez. 1984.
Botulismo en el lactante, una nueva enfermedad. Arch. Arg. Pediatr. 82:
197–198.
22. Long, S. S. 1985. Epidemiologic study of infant botulism in Pennsylvania:
report of the Infant Botulism Study Group. Pediatrics 75:928–934.
23. Long, S. S. 2007. Infant botulism and treatment with BIG-IV (BabyBIG).
Pediatr. Infect. Dis. J. 26:261–262.
24. Lu´quez, C., et al. 2005. Distribution of botulinum toxin-producing clostridia
in soils of Argentina. Appl. Environ. Microbiol. 71:4137–4139.
25. Lu´quez, C., et al. 2007. Relationship between the incidence of infant botu-
1848 VANELLA DE CUETOS ET AL. CLIN.VACCINE IMMUNOL.
on November 12, 2011 by guesthttp://cvi.asm.org/Downloaded from
lism and the presence of botulinum toxin-producing clostridia in the soil of
Argentina, 1982–2005. J. Pediatr. Neurol. 5:279–286.
26. McCroskey, L. M., C. L. Hatheway, L. Fenicia, B. Pasolini, and P. Aureli.
1986. Characterization of an organism that produces type E botulinal toxin
but which resembles Clostridium butyricum from the feces of an infant with
type E botulism. J. Clin. Microbiol. 23:201–202.
27. Midura, T. F. 1996. Update: infant botulism. Clin. Microbiol. Rev. 9:119–125.
28. Satorres, S. E., L. E. Alcara´z, R. A. Ferna´ndez, and O. N. Centorbi. 1999.
Isolation of Clostridium botulinum in medicinal plants. Anaerobe 5:173–175.
29. Sobel, J. 2005. Botulism. Clin. Infect. Dis. 41:1167–1173.
30. Spika, J. S., et al. 1989. Risk factors for infant botulism in the United States.
Am. J. Dis. Child. 143:828–832.
VOL. 18, 2011 EQUINE ANTITOXIN FOR INFANT BOTULISM TREATMENT 1849
on November 12, 2011 by guesthttp://cvi.asm.org/Downloaded from
