Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021.

Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.

Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic.

Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.

Pediatric Botulism and Use of Equine Botulinum Antitoxin in Children: A Systematic Review.

Background: Botulism manifests with cranial nerve palsies and flaccid paralysis in children and adults. Botulism must be rapidly identified and treated; however, clinical presentation and treatment outcomes of noninfant botulism in children are not well described. Methods: We searched 12 databases for peer-reviewed and non-peer-reviewed reports with primary data on botulism in children (persons <18 years of age) or botulinum antitoxin administration to children. Reports underwent title and abstract screening and full text review. For each case, patient demographic, clinical, and outcome data were abstracted. Results: Of 7065 reports identified, 184 met inclusion criteria and described 360 pediatric botulism cases (79% confirmed, 21% probable) that occurred during 1929-2015 in 34 countries. Fifty-three percent were male; age ranged from 4 months to 17 years (median, 10 years). The most commonly reported signs and symptoms were dysphagia (53%), dysarthria (39%), and generalized weakness (37%). Inpatient length of stay ranged from 1 to 425 days (median, 24 days); 14% of cases required intensive care unit admission; 25% reported mechanical ventilation. Eighty-three (23%) children died. Median interval from illness onset to death was 1 day (range, 0-260 days). Among patients who received antitoxin (n = 193), 23 (12%) reported an adverse event, including rash, fever, serum sickness, and anaphylaxis. Relative risk of death among patients treated with antitoxin compared with patients not treated with antitoxin was 0.24 (95% confidence interval, .14-.40; P < .0001). Conclusions: Dysphagia and dysarthria were the most commonly reported cranial nerve symptoms in children with botulism; generalized weakness was described more than paralysis. Children who received antitoxin had better survival; serious adverse events were rare. Most deaths occurred early in the clinical course; therefore, botulism in children should be identified and treated rapidly.

Clinical Features of Foodborne and Wound Botulism: A Systematic Review of the Literature, 1932-2015.

Background: Botulism is a rare, potentially fatal paralytic illness caused by neurotoxins. To inform the evaluation of patients with suspected botulism, we conducted a systematic review to describe the clinical features of botulism. Methods: We searched Medline Ovid, Embase Dialog, Embase Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Global Health Ovid, Cochrane Library, Scopus, and ClinicalTrials.gov for English language articles through May 2015. Information abstracted included demographics, signs and symptoms, laboratory results, and clinical outcome for foodborne and wound botulism patients confirmed by laboratory testing, epidemiologic link, or association with an outbreak. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42015024784). Results: We identified 402 patients from 233 articles published in English between 1932 and 2015. Most cases (n = 346 [86%]) were foodborne botulism and most (n = 263 [65%]) were associated with an outbreak. The median incubation period was 1 day, and the median time from illness onset to hospital admission was 2 days. Shortness of breath, dyspnea, or respiratory distress or failure at hospital admission was reported in 169 (42%) patients; 71 (42%) reported respiratory involvement without report of extremity weakness. Among 154 patients for whom the hospital day of intubation was reported, 134 (87%) were intubated on the first or second hospital day. Conclusions: Botulism patients can experience a range of signs and symptoms. Respiratory involvement may occur early in the illness and can occur without preceding extremity weakness. Clinicians and public health departments preparing for and responding to botulism events should use this information to guide the evaluation of suspected botulism patients.

Clinical Criteria to Trigger Suspicion for Botulism: An Evidence-Based Tool to Facilitate Timely Recognition of Suspected Cases During Sporadic Events and Outbreaks.

Effective treatment for botulism requires early clinical recognition. Diagnosis of botulism, including during outbreaks, can be challenging. We assessed combinations of signs and symptoms among confirmed cases and identified sensitive clinical criteria to trigger suspicion. We produced a tool that may facilitate rapid identification of sporadic and outbreak-associated cases.

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.

Background: Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods: We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results: Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Conclusions: Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin.

Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods: From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results: Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

The Epidemiology of Foodborne Botulism Outbreaks: A Systematic Review.

Background: We performed a systematic review of foodborne botulism outbreaks to describe their clinical aspects and descriptive epidemiology in order to inform public health response strategies. Methods: We searched seven databases for reports of foodborne botulism outbreaks published in English from database inception to May 2015. We summarized descriptive characteristics and analyzed differences in exposure and toxin types by geographic region. We performed logistic regression to assess correlations between exposure source, implicated food, and outbreak size. Results: There were 197 outbreaks reported between 1920 and 2014. The median number of cases per outbreak was 3 (range 2-97). The majority of reported outbreaks (109; 55%) occurred in the United States. Toxin types A, B, E, and F were identified as the causative agent in 34%, 16%, 17%, and 1% of outbreaks, respectively. The median duration between exposure and symptom onset was approximately 1 day. The mean percentage of cases requiring mechanical ventilation per outbreak was 34%. Seventy percent of all outbreaks and 77% of small outbreaks (≤11 cases) originated from point source exposures, while commercial foods were significantly (odds ratio, 6.9; 95% confidence interval, 2.2-21.1) associated with large outbreaks (≥12 cases). Conclusions: Toxin type A accounted for half of outbreaks, and these outbreaks had a higher proportion of patient ventilatory failure. Most outbreaks were due to point source exposures, while outbreaks due to commercial food were larger. For effective responses to foodborne botulism outbreaks, these findings demonstrate the need for timely outbreak investigation and hospital surge capacity.

Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923-2016.

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.

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

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

CDC Safety Training Course for Ebola Virus Disease Healthcare Workers.

Response to sudden epidemic infectious disease emergencies can demand intensive and specialized training, as demonstrated in 2014 when Ebola virus disease (EVD) rapidly spread throughout West Africa. The medical community quickly became overwhelmed because of limited staff, supplies, and Ebola treatment units (ETUs). Because a mechanism to rapidly increase trained healthcare workers was needed, the US Centers for Disease Control and Prevention developed and implemented an introductory EVD safety training course to prepare US healthcare workers to work in West Africa ETUs. The goal was to teach principles and practices of safely providing patient care and was delivered through lectures, small-group breakout sessions, and practical exercises. During September 2014-March 2015, a total of 570 participants were trained during 16 course sessions. This course quickly increased the number of clinicians who could provide care in West Africa ETUs, showing the feasibility of rapidly developing and implementing training in response to a public health emergency.

Low-Cost National Media-Based Surveillance System for Public Health Events, Bangladesh.

We assessed a media-based public health surveillance system in Bangladesh during 2010-2011. The system is a highly effective, low-cost, locally appropriate, and sustainable outbreak detection tool that could be used in other low-income, resource-poor settings to meet the capacity for surveillance outlined in the International Health Regulations 2005.

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities.

Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug-resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.

Integrating genome-based informatics to modernize global disease monitoring, information sharing, and response.

The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.

Epidemiologic investigation of an occupational illness of tobacco harvesters in southern Brazil, a worldwide leader in tobacco production.

OBJECTIVES: As part of smoking surveillance, the authors conducted an epidemiologic investigation in southern Brazil to identify the occurrence of Green Tobacco Sickness and risk factors for illness and to recommend control and prevention measures. METHODS: A 1:2 case-control study matched by subjects' smoking habits. The study population was residents of Candelária, Rio Grande do Sul state, who farm tobacco and provided a urine sample for cotinine measurement by high-performance liquid chromatography. Confirmed cases were persons with compatible clinical presentation (headache, nausea, vomit, dizziness or weakness) and cotinine level >10 ng/ml. Controls were persons without compatible signs or symptoms. The association measure was the matched OR with 95% CIs and p<0.05. RESULTS: Of 33 confirmed cases, 64% were men, average age was 33 years (SD ± 11.8 years) and 57% were landowners. Cases have had similar illness in the past and were likelier to be workers hired by farmers-landowners than controls. Multivariate analysis yielded independent association between these variables and illness, controlled for age and sex. Contact with pesticides and working with wet tobacco leaves were not associated with illness. CONCLUSIONS: The authors confirmed Green Tobacco Sickness in southern Brazil; the authors recommend investigation of its prevalence in tobacco-growing regions and monitoring of and education about the disease and its prevention by occupational health authorities.

Rapid development and use of a nationwide training program for cholera management, Haiti, 2010.

When epidemic cholera appeared in Haiti in October 2010, the medical community there had virtually no experience with the disease and needed rapid training as the epidemic spread throughout the country. We developed a set of training materials specific to Haiti and launched a cascading training effort. Through a training-of-trainers course in November 14-15, 2010, and department-level training conducted in French and Creole over the following 3 weeks, 521 persons were trained and equipped to further train staff at the institutions where they worked. After the training, the hospitalized cholera patients' case-fatality rate dropped from 4% to <2% by mid-December and was <1% by January 2011. Continuing in-service training, monitoring and evaluation, and integration of cholera management into regular clinical training will help sustain this success.

Evaluation of pot-chlorination of wells during a cholera outbreak, Bissau, Guinea-Bissau, 2008.

We evaluated the ability of UNICEF-designed pot-chlorinators to achieve recommended free residual chlorine (FRC) levels in well water in Bissau, Guinea-Bissau, during a cholera outbreak. Thirty wells were randomly selected from six neighbourhoods. Pot-chlorinators--perforated plastic bottles filled with gravel, sand and calcium hypochlorite granules--were placed in each well. FRC was measured before and 24, 48 and 72 h after placement and compared with World Health Organization (WHO)-recommended levels of 21 mg L(-1) for well water during cholera outbreaks and 0.2-5 mg L 1 in non-outbreak settings. Presence of well covers, distance from wells to latrines, and rainfall were noted. Complete post-chlorination data were collected from 26 wells. At baseline, no wells had FRC>0.09 mg L(-1). At 24, 48 and 72 h post-chlorination, 4 (15%), 1 (4%) and 0 wells had FRC>or=1 mg L(-1) and 16 (62%), 4 (15%) and 1 (4%) wells had FRC between 0.2 and 5 mg L(-1), respectively. Several families reported discontinuing household water chlorination after wells were treated with pot-chlorinators. Pot-chlorinators failed to achieve WHO-recommended FRC levels in well water during a cholera outbreak, and conveyed a false sense of security to local residents. Pot-chlorination should be discouraged and alternative approaches to well-water disinfection promoted.

Foodborne Botulism Outbreaks in the United States, 2001-2017.

Foodborne botulism is an intoxication caused by ingestion of food containing botulinum neurotoxin. Cases of foodborne botulism are usually sporadic (single, unrelated) but outbreaks of two or more cases occur. In this mini-review we will examine the following for the period 2001-2017, in the United States: botulism surveillance data, outbreaks of botulism affecting 10 or more people, and the public health preparedness and response approach.

Clinical recovery and circulating botulinum toxin type F in adult patient.

A 56-year-old woman in Helena, Montana, USA, who showed clinical signs of paralysis, received antitoxins to botulinum toxins A, B, and E within 24 hours; nevertheless, symptoms progressed to complete quadriplegia. On day 8, she began moving spontaneously, even though blood tests later showed botulinum toxin type F remained.