Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923–2016
Systematic Review of Botulism Treatment • CID
Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta- analysis of Cases, 1923-2016
John C. O'Horo 0 1 2
Eugene P. Harper 5
Abdelghani El Rafei 2
Rashid Ali 0 1
Daniel C. DeSimone 2
Amra Sakusic 0 1
Omar M. Abu Saleh 2
Jasmine R. Marcelin 2
Eugene M. Tan 2
Agam K. Rao 4
Jeremy Sobel 3
Pritish K. Tosh 2
0 Department of Medicine, Division of Pulmonary and Critical Care Medicine
1 Multidisciplinary Epidemiology and Translational Research in Critical Care, Emergency and Perioperative Medicine Group
2 Department of Medicine, Division of Infectious Diseases
3 DFWED, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention , Atlanta , Georgia
4 Enteric Diseases Epidemiology Branch, Division of Foodborne , Waterborne, and Environmental Diseases, DFWED
5 School of Medicine, Mayo Clinic , Rochester, Minnesota , USA
Background. Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods. We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results. We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions. Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.
Botulism is a rare neuroparalytic illness characterized by bilateral
cranial nerve palsies and descending paralysis, which may lead
to respiratory failure. Disease can be fatal, particularly without
treatment. Botulinum neurotoxin (BoNT) mediates the effects of
]. Foodborne botulism occurs following ingestion of
toxin found in contaminated foods; outbreaks occur periodically,
and contamination of a widely consumed food could cause many
illnesses. BoNT is the most toxic substance by weight known, and
various countries with biologic warfare programs have weaponized
it as a biological weapon. The Centers for Disease Control and
Prevention classifies BoNT as a category A biological agent [
Seven botulism toxin serotypes, A–G, were described between
1919 and 1970. Most human botulism is caused by serotypes
A, B, E, and F, but others have pathogenic potential as well.
Paralysis induced by BoNT can last weeks to months. In cases in
which the respiratory tract or respiratory muscles are impaired,
mechanical ventilation is life-saving. Botulinum antitoxins can
neutralize circulating botulinum toxin, preventing toxin
binding to the neuromuscular junction, but does not reverse existing
paralysis. The mainstays of treatment are supportive care and
botulinum antitoxin. These measures have been credited with
reducing botulism mortality in the United States from >60%
in the early 20th century to <5% at present [
other targeted treatments have been attempted to ameliorate the
effects of botulism, such as cathartics and enemas to clear toxin
from the gastrointestinal tract, and guanidine and
3,4-diaminopuridine to stimulate acetylcholine release [
Equine-source botulism antitoxins of varying valencies
(anti-A, anti-B, anti-AB, etc) and neutralizing capacities have
been used over the past century. Currently, the sole botulinum
antitoxin product licensed for treatment of noninfant botulism
in the United States is equine-source botulism antitoxin
]. A human-source antitoxin, botulism immune globulin
intravenous (BIG-IV), is licensed in the United States solely for
the treatment for infants with botulism type A or type B.
Botulism is rare, with <100 noninfant cases and approximately
100 infant cases reported annually in the United States [
Consequently, peer-reviewed studies on the efficacy of botulinum
antitoxin are sparse. In nearly a century, only 1 study, involving a
retrospective cohort, examined the effectiveness of equine-origin
botulinum antitoxin, finding reduced mortality and other
measures of severity associated with early treatment [
]. For infant
botulism, 1 randomized controlled trial found that use of BIG-IV
was associated with reduced duration of mechanical ventilation
and hospitalization without reported adverse events [
A large botulism outbreak, either naturally occurring or
intentionally created, may strain resources, and at present, no
evidence-based guidance exists to prioritize antitoxin
administration. Data-based treatment recommendations are needed
to ensure an effective and efficient public health response. We
sought to systematically review all published reports and
studies on the treatment of foodborne botulism. The questions that
guided our systematic review were (1) what benefit should be
expected from botulinum antitoxin? (2) Is there a window of
time beyond which administration of antitoxin is no longer
beneficial? (3) Do any patient demographic or clinical
characteristics predict greater benefit from antitoxin administration?
This study was registered on the International
Prospective Register of Systematic Reviews (PROSPERO;
CRD42015024327). Our systematic review was conducted in
accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines [
With the assistance of an expert research librarian, we
queried PubMed via Medline, Web of Science, Embase, Ovid, and
Cumulative Index to Nursing and Allied Health Literature
(CINAHL) using keywords such as botulism, Clostridium
botulinum, botulinum antitoxin, botulism, botulinum, BoNT,
antibacterial agents, antitoxins, botulinum antitoxin, respiration
artificial, activated charcoal, cholinergic antagonists, drugs
investigational, disaster planning, immunoglobulins,
cholinergic, guanidine, anticholinergic, ventilation, antitoxin, antisera,
antiserum, antibody, antibiotic, charcoal, pharmaceutical,
germine, immunoglobulin, intubation, experimental animal, and
nonhuman; the search strategy is detailed in Supplementary
Appendix 1. Embase, Scopus, Medline, CINAHL contain
conference proceedings and dissertations). Additionally we
searched National Technical Information Service, Defense
Technical Information Center, and Google Scholar for
government documents, and manually included article references for
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Inclusion and Exclusion Criteria
We included any article in the English language including case
report, series, cohort, controlled trial, and animal study that
reported patient-level data on the natural history of foodborne
botulism or the effect of a directed treatment such as antitoxin.
Botulism was defined by clinical diagnosis, epidemiologically
(reported exposure known source with neurologic symptoms
of botulism), or based on laboratory assays. Because of different
pathophysiology, human cases of iatrogenic, infant, and wound
botulism were excluded. Animal cases were excluded if they
did not describe both controlled toxin exposure and antitoxin
treatment. Case reports and series of <3 cases were abstracted
for descriptive analysis, including specific rare treatments and
outcomes, and excluded from meta-analysis and formal
Article Screening and Abstraction
Articles were screened independently by 2 investigators (J.
C. O. and P. K. T.) using Covidence (www.covidence.org), an
online tool for systematic reviews. Initial screening entailed
abstract review, followed by review of all potentially relevant
full text articles. Reviewers determined if cases reported a
case of foodborne botulism with discussion of both
treatment strategies and clinical outcomes; if these criteria were
met, the study was included. In both phases, disagreements
were resolved by discussion and consensus was reached on all
Articles were abstracted using a standardized form
developed on Research Electronic Data Capture (REDCap)
(Supplementary Appendix 2). Study data were collected and
managed using REDCap electronic data capture tools hosted
at Mayo Clinic. REDCap is a secure, web-based application
designed to support data capture for research studies, providing
(1) an intuitive interface for validated data entry; (2) audit trails
for tracking data manipulation and export procedures; (3)
automated export procedures for seamless data downloads to
common statistical packages; and (4) procedures for importing data
from external sources [
]. Primary abstraction was completed
by 1 of 8 reviewers (E. H., A. G. E. L., R. A., D. D., A. S., O. A.,
J. M., or E. T.) trained in use of the abstraction tool and
definitions by 1 investigator (J. C. O.). All articles were independently
abstracted and reviewed by a second reviewer (J. C. O. or P. K.
T.). Disagreements were resolved through discussion at weekly
Articles were reviewed for outcomes including mortality,
hospital length of stay, duration of mechanical ventilation, and
longterm neurologic sequelae. Articles were grouped first by the
article type (case series, cohorts and trials, animal studies) and
then by the intervention (eg, monovalent, bivalent, heptavalent
For meta-analytic purposes, we combined cohort studies,
outbreak reports, or case series with N ≥3 to estimate the effect of
antitoxin on mortality, ventilation, and hospital length of stay.
In studies in which both the toxin type and antitoxin type were
reported, only patients who received antitoxin which matched
identified toxin exposures were considered “treated.”
For mortality analysis, the odds of death were calculated as a
proportion of the total number of treated vs not-treated patients
in a given report. Because in smaller studies the binomial
distribution may not approximate the normal distribution, we performed
a double arcsine Freeman-Tukey transformation to stabilize the
variance and restore assumptions of normalcy. We calculated
estimated variance by adding a proportionality constant to the
observed number of deaths to adjust for zero values; this was
equal to the reciprocal of the total number of subjects in the study.
Resultant data were combined using the random-effects model
prescribed by DerSimonian and Laird [
]. Subgroup analyses
were performed by antitoxin type and toxin types. The odds of
death for each type was calculated and compared. Heterogeneity
was assessed using I2, where 0% indicates low heterogeneity and
100% high heterogeneity. Publication bias was assessed using
visual inspection of a funnel plot using the method prescribed
by Egger et al [
]. Statistical analysis was performed using Stata
(StataCorp, College Station, Texas) and Review Manager 5 (Nordic
Cochrane Center, Copenhagen, Denmark) software.
Duration of hospitalization and ventilation were modeled
using mean and standard deviation data from cohorts and case
series providing sufficient data to determine patients’ duration
of treatment. On meta-analysis, only studies including both
treated and untreated patients were analyzed, as interhospital
ventilation and extubation practices were too great for indirect
Early vs late administration of antitoxin, defined by report
authors, was analyzed relative to mortality, duration of
ventilation, and duration of hospitalization using the methods
described above. Subgroups were defined by (1) definitions
given in the study for early vs late (Supplementary Appendix
8) or (2) patients who received antitoxin within 24 hours of
presenting for medical care vs all others. Additional sensitivity
analyses were performed on studies with sufficient patient-level data
to exclude those who died when calculating length of stay and
duration of hospitalization. This was performed to determine
the effect of any survivor bias on these time-dependent variables.
Finally, using study evidence ratings, we conducted an additional
sensitivity analysis excluding the 50% lowest-scoring studies as
rated by the evidence-rating tool described below. Results from
these sensitivity analyses were compared to the main outcomes
to identify confounding by reporting and publication bias.
Meta-regression was performed on all studies by year of
publication to determine the role that evolving supportive care
techniques have played over time in each of these domains.
Individual Study Evidence Rating
Each publication was assessed by both reviewers for quality of
evidence using a tool developed by the authors (Supplementary
Appendix 3). This tool evaluates articles for design quality,
level of certainty, and completeness of reporting. Study design
and evidence were modified from the criteria used by the
US Preventive Services Task Force. The risk-of-bias tool was
modified from the Newcastle-Ottawa Scale. Completeness
was assessed based on the presence of 15 pieces of
information deemed pertinent to a botulism treatment article
(Supplementary Appendix 3).
The search strategy yielded 13 055 distinct abstracts for
screening. One abstract could not be obtained; 13 069 were screened,
of which 12 455 studies were excluded. Full text evaluation was
performed on 599 articles, of which 223 met inclusion criteria
(Figure 1). Characteristics of the comparative studies included
are described in Supplementary Appendix 7. Outcomes are
summarized in Table 1. Additional details on the method of
diagnosis are shown in Supplementary Appendix 8. Individual
studies and case reports unsuitable for quantitative analysis are
summarized in Table 2.
Data tying individual outcomes to age, gender/sex,
comorbidities, and severity of illness at time of initial contact with medical
care were reported inconsistently. While we cannot exclude that
some populations may receive greater benefit from antitoxin
treatment, we could not identify such a subpopulation on the
basis of the highly limited data set.
All articles that described survival alluded to the importance
of high-quality supportive care, particularly respiratory
critical care. However, insufficient detail (eg, modes of
mechanical ventilation and nutritional support) in these publications
precluded evaluation of specific intensive care components on
Relationship Between Type of Toxin and Clinical Outcome
Mortality among patients treated and not treated with
antitoxin, by toxin type, is presented in Figures 2–5. Overall,
antitoxin reduced mortality (odds ratio [OR], 0.22; 95% confidence
interval [CI], .17–.29); a high degree of heterogeneity was
observed (I2 = 69.3%). Heterogeneity was largely due to
studies not reporting toxin type (Figure 2). Subset analyses by toxin
type were significantly less heterogeneous as described below.
On meta-regression modeling, study year, design, selection,
comparability, and completeness variables were not substantial
contributors to heterogeneity (P = 0.86). Egger test identified no
evidence of publication bias (P = 0.26).
Systematic Review of Botulism Treatment • CID 2018:66 (Suppl 1) • S45
The greatest reduction in botulism-related mortality was
associated with the use of type E antitoxin (OR, 0.13; 95% CI,
.06–.30; I2 = 10%; Figure 5), followed by type A antitoxin (OR,
0.57; 95% CI, .39–.84; I2 = 81.2%; Figure 3); reduction in
mortality was not statistically significant for type B antitoxin (OR,
0.74; 95% CI, .27–1.97; Figure 4). Key data on the impact of
type E antitoxin come from Dolman and Iida, who examined
Canadian mortality rates of botulism type E before (baseline)
and after introduction of type E antitoxin therapy [
mortality in this study was derived from secondary data and
was thus excluded from the meta-analysis. Dolman and Iida’s
baseline was derived from 75 outbreaks with 374 patients in
6 countries; case fatality rate was 30%. In Canada, in 28
outbreaks, 85 of 220 patients were treated with anti-E antitoxin.
S46 • CID 2018:66 (Suppl 1) • O’Horo et al
Among patients not treated with antitoxin, 28.9% died,
compared with 3.5% of those treated [
Use of Different Antitoxin Formulations
Studies that reported both toxin type and administered
antitoxin type were less heterogeneous overall and demonstrated
a survival benefit to antitoxin (OR, 0.16; .09–.30; I2 = 0%;
Figure 6). Fifteen studies reported use of trivalent antitoxin, 10
bivalent antitoxin, and 2 heptavalent antitoxin.
Use of anti-ABE trivalent antitoxin was most commonly
]. Trivalent antitoxin, when administered in
cases of botulism types A, B, or E, reduced mortality (OR, 0.13;
95% CI, .04–.38; I2 = 0%). Side effects from this formulation
were less commonly reported than all other antitoxins with side
effects reported. Anti-ABE antitoxin was generally reported
as effective and well tolerated. Case series reported occasional
residual neuromuscular deficits persisting up to several months
after therapy (Table 2).
Bivalent AB antitoxin was the second most commonly
reported formulation [
]; its use was not significantly
associated with reduction in mortality (OR, 0.37; 95% CI, .10–
1.31; I2 = 0%). Information on heptavalent antitoxin includes 2
reports of foodborne botulism outbreaks. One was caused by
toxin type A–contaminated canned bamboo in Thailand [
] and affected 137 patients, of whom 20 were treated with
heptavalent antitoxin, and the others with bivalent AB or
quadrivalent ABEF antitoxin. No deaths were reported. The second
outbreak, caused by type A toxin, affected 8 prison inmates in
Utah . All received heptavalent antitoxin; none died. Low
mortality in both outbreaks was attributed to excellent critical
and supportive care of the patients [
The largest available data source on heptavalent antitoxin was
the unpublished Centers for Disease Control and Prevention’s
expanded-access Investigational New Drug application. Data
included mostly foodborne botulism cases and several cases of
wound botulism, infant botulism, and other syndromes. Of 249
patients treated under this protocol, 105 were confirmed as
having botulism. One child experienced hemodynamic instability
after administration, comprising the only serious adverse event
seen with heptavalent antitoxin. Allergic reactions, typically
rash, were noted in 6 patients, all of whom recovered without
sequelae. Seven deaths were observed in confirmed botulism
cases treated with heptavalent antitoxin; none were attributed
to the antitoxin [
A variety of other antitoxin combinations are reported
in Figure 6, including quadrivalent ABEF [
], monovalent E [
], and a combination of bivalent
AB formulation and monovalent E formulation [
small number of deaths from botulism reported in patients
treated with these agents precludes a statistical assessment of
their impact on clinical outcomes.
tor dependence compared with those receiving it on day 6 [
Sheth et al reported on 6 patients in a botulism type B
outbreak associated with bottled carrot juice. Five patients received
antitoxin: 3 within 24 hours, 1 on day 13, and 1 on day 45. At the
time of publication, 2 patients had been ventilator dependent
for >1 year [
]. We treated these patients as having 365
ventilator-days, demonstrating some reduction in ventilator time in
those who had early treatment.
mechanical ventilation was significantly reduced and there were
no deaths, compared with 7 deaths among patients treated later.
Overall, earlier antitoxin administration reduced mortality,
compared with later administration (OR, 0.12; 95% CI, .03–.41;
I2 = 0%; Figure 7).
In general, animal studies showed some benefit to antitoxin
treatment (Supplementary Appendices 5 and 9).
Therapeutic Agents Other Than Antitoxin
We identified no improvement with several agents reported in
the literature (Supplementary Appendix 6).
Yu et al also reported a benefit from heptavalent antitoxin
Study Quality Assessments
given within 48 hours compared with later administration [
Most studies were rated as level III evidence (case reports and
In patients treated early, the proportion of patients requiring
series, opinions of expert authorities) (Supplementary Appendix
S48 • CID 2018:66 (Suppl 1) • O’Horo et al
4). Outcome assessments were not consistently high quality,
with a mean of 5/12 on our scoring rubric. Completeness of
reporting was generally good, with an average score of 11/16.
Study design was not a major contributor to interobserver
variability (P = .50). Study outcome assessments were similarly
not a major contributor (P = .54). Completeness was also not
significantly associated on meta-regression (P = .31).
In this systematic, comprehensive literature review of botulism
treatment, we examined all relevant publications since the early
20th century. Our findings support the routine administration
of botulinum antitoxin to botulism patients. Antitoxin
treatment reduces mortality, and the available data show that earlier
antitoxin administration reduces both mortality and
ventilation time, compared with later administration. However,
there are reports of benefit even with late antitoxin
administration, defined by the authors as anywhere from >24 hours
after illness onset to 48 hours after presentation. We found no
clear indication of a point in the course of illness at which
antitoxin administration was no longer beneficial. Although the
nature of the data did not allow for quantitative analysis of the
benefits of supportive care, this modality is doubtless essential
to survival of patients with severe botulism, as evidenced by
decreased mortality since the introduction of ventilator care in
the 1960s. Despite some early promising studies for guanidine,
we did not identify clear or sustained benefit to any alternative
treatment modalities applied to botulism patients.
Qualitative studies and case reports broadly supported
treatment with botulinum antitoxin. Several older studies dating
to the first half of the 20th century reported dramatic clinical
resolution following antitoxin administration with all types
(Table 2); the significance of these observations is unclear. It is
worth noting that while mortality in patients not treated with
antitoxin was high, often these patients did not have access to
advanced life support. Therefore, these poor outcomes were
likely influenced by the lack of supportive care.
Available data do not suggest any patient characteristics that
predict a response to therapy. Because the data do not provide
evidence of demographic or clinical indicators for predictors of
better outcome, we cannot recommend any specific criteria for
prioritizing antitoxin treatment when its availability is limited.
Further study is needed to risk-stratify patients and identify
patients likeliest to benefit from antitoxin treatment.
Correspondence between toxin types and antitoxin serotype
corresponded with clinical outcome. The currently licensed
heptavalent antitoxin provides appropriate treatment for
botulism caused by serotypes A–G. Data available to us were
limited to unpublished prelicensure surveillance. Therefore,
treatment outcomes should be monitored and analyzed on an
Recently, reports of new toxin types have been published,
including a novel toxin subsequently shown to be a hybrid
type A/F fully neutralized by HBAT [
] and a novel toxin
S52 • CID 2018:66 (Suppl 1) • O’Horo et al
identified and assembled from the published gene sequence of
a C. botulinum isolate . These reports illustrate important
challenges in the field of botulism. New botulinum toxins of
clinical significance may be discovered. The routine analysis
and dissemination of clostridial gene sequences can
accelerate such discoveries, and likely facilitate assembly of toxins, for
purposes hopefully benign but possibly nefarious. Preparedness
requires careful laboratory investigation of all suspected
botulism cases and ongoing research and development of new
Appropriate supportive care is considered a cornerstone in
survival and recovery from botulism [
]. It must be borne
in mind that a substantial proportion of botulism patients
suffer respiratory compromise, some despite prompt diagnosis
and early antitoxin treatment; therefore, survival of some
botulism patients, treated or untreated with antitoxin, depends on
high-quality intensive care. Longstanding experience shows
that deaths from botulism can be averted by providing
meticulous intensive care, including ventilator care when required
. Antitoxin should be given as soon as possible along with
meticulous intensive care. Likewise, mortality in case series and
reports was highest in patients remote from hospital or
emergency care facilities. Early recognition and best intensive care
unit practices are an important part of the comprehensive care
of the botulism patient. In a situation of limited antitoxin
availability, the availability of critical supportive care will determine
survival for patients experiencing respiratory compromise.
Critical care is an essential component of emergency
preparedness for botulism events, both naturally occurring and
Our study has several limitations. We did not include reports of
wound botulism in the review, so our findings may not fully apply
to that syndrome. Although we made every effort to separate
outbreaks and case reports to avoid analyzing the same individual
twice, the way that outbreaks are reported and analyzed,
particularly in older literature, makes this nearly impossible. For example,
several patients are likely reported in each of 2 case series reported
by Dolman [
] likely, but it is impossible to determine which.
We attempted to account for this with several sensitivity analyses
serially excluding these and other high overlap studies; we did not
see a substantial change in our overall results.
Our review includes publications spanning 8 decades.
Aside from improvements in antitoxin manufacture, types,
and valence, this period encompasses dramatic improvements
in supportive care technology and techniques and the rise of
critical care as a specialty. The effect of these on outcomes
is profound, but we could not methodologically account for
it in our results. We must therefore accept that some of the
benefit attributed to antitoxin may in fact be due to some of
these advances. Thus, we cautiously interpret our results to
suggest that appropriate antitoxin therapy in conjunction with
high-quality supportive care produce the best outcomes in
A final limitation is our inability to adjust for the effect of
disease progression and timing. Although we did observe some
benefit from early antitoxin administration as defined by the
report authors, several confounders are inherent in this
finding. First, early administration may have been a marker for
early recognition and initiation of other interventions. Second,
early administration in several studies may have reflected early
Systematic Review of Botulism Treatment • CID 2018:66 (Suppl 1) • S53
treatment of clinically milder cases that presented after delayed
diagnosis of a severely ill outbreak index case. However, a
beneficial effect of early antitoxin administration was reported in
nearly all studies examining this measure. Overall, this would
support a benefit of earlier administration, but we may have
overestimated the degree of benefit.
Another significant limitation is our focus on foodborne
botulism. This was done primarily because of the different
physiology involved in foodborne, infant, and iatrogenic
botulism, and allowed us to focus on a less heterogenous
population experiencing the most common form of
botulism. We do not know how these findings may apply to other
forms of botulism.
In conclusion, we found that early administration of
antitoxin of serotype-appropriate antitoxin, along with high-quality
supportive care, was consistently associated with reduced
mortality in botulism patients. No demographic or clinical
predictors of the response to antitoxin were identified.
Acknowledgments. We gratefully acknowledge the contribution of
Joanne Taliano, CDC librarian, for her role in developing and executing
the systematic review literature search; and Elliott Churchill, for expert
Disclaimer. The contents of this work are solely the responsibility
of the authors and do not necessarily represent the official views of the
National Institutes of Health (NIH) or the Centers for Disease Control and
Prevention (CDC). The inclusion of commercial product or entity names
is for identification purposes only and does not constitute endorsement by
NIH or CDC.
Financial support. This work was supported in part by the National
Center for Advancing Translational Sciences (grant number UL1
TR000135). J. C. O.’s time was supported by the Robert D. and Patricia
E. Kern Center for the Science of Health Care Delivery at Mayo Clinic.
S54 • CID 2018:66 (Suppl 1) • O’Horo et al
Supplement sponsorship. This article appears as part of the
supplement “Botulism,” sponsored by the Centers for Disease Control and
Potential conflicts of interest. All authors: No potential conflicts of
interest. All authors have submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest. Conflicts that the editors consider relevant to
the content of the manuscript have been disclosed.
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