Wound Botulism Among Persons Who Inject Black Tar Heroin in New Mexico, 2016

Outbreaks of wound botulism are rare, but clinicians and health departments should maintain suspicion for signs, symptoms, and risk factors of wound botulism among persons who inject drugs in order to initiate treatment quickly. This report describes an outbreak of three wound botulism cases among persons in two adjacent counties who injected drugs. Provisional information about these cases was previously published in the CDC National Botulism Surveillance Summary. All three cases in this outbreak were laboratory-confirmed, including one case with detection of botulinum toxin type A in a wound culture sample taken 43 days after last possible heroin exposure. Findings highlight the delay in diagnosis which led to prolonged hospitalization and the persistence of botulinum toxin in one patient.

Treatment of venous ulcers in drug addicts: A case report

Venous ulcers are common in drug addicts and, although the management of these wounds is the same as in other patients, there are differences in the approach and the outcome of treatment. Those injecting drugs are at risk of serious infections, such as necrotizing fasciitis, wound botulism, and cutaneous anthrax due to the nature of the substances being injected. Herein, we present two cases of venous ulcers in drug addicts in their thirties. Both patients had been suffering from a venous ulcer for several years and the final result differed in the two patients. We concluded that it is necessary to raise awareness of the importance of treatment and lifestyle changes. The multidisciplinary approach in these patients may contribute to the improvement of wound healing.

Botulinum Neurotoxins (BoNTs) and Their Biological, Pharmacological, and Toxicological Issues: A Scoping Review

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod-shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C.botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action.

Early diagnosis and critical management of wound botulism in the emergency department: a single center experience and literature review

Background Clostridium botulinum remains a major threat to a select population of subcutaneous and intramuscular drug users. We conducted a retrospective study of patients who were diagnosed with wound botulism and their clinical presentations to the Emergency Department (ED). Results A total of 21 patients met the inclusion criteria and all had a confirmed history of heroin use disorder. Initial presentation to the ED included generalized weakness (n = 20, 95%), difficulty swallowing (n = 15, 71%), and speech/voice problems (n = 14, 79%). Sixteen patients (76%) also presented with visible skin wounds and fifteen (71%) required mechanical ventilation (MV). Patients who presented with dysphagia as well as dysarthria and/or dysphonia were more likely to require a percutaneous endoscopic gastrostomy (PEG) tube. Patients who required MV and PEG tubes were noted to have a longer hospital length of stay (LOS) due to the severity of the disease progression. Conclusions Emergency physicians should remain vigilant about early recognition of wound botulism, especially in patients who inject drugs.

Clostridium botulinum Type B Isolated From a Wound Botulism Case Due to Injection Drug Use Resembles Other Local Strains Originating From Hawaii

Clostridium botulinum produces botulinum neurotoxin (BoNT), which can lead to death if untreated. In the United States, over 90% of wound botulism cases are associated with injection drug use of black tar heroin. We sought to determine the phylogenetic relatedness of C. botulinum isolated from an injection drug use wound botulism case and isolates from endogenous infant botulism cases in Hawaii. Nineteen C. botulinum type B isolates from Hawaii and one type B isolate from California were analyzed by whole-genome sequencing. The botulinum toxin gene (bont) subtype was determined using CLC Genomics Workbench, and the seven-gene multi-locus sequence type (MLST) was identified by querying PubMLST. Mashtree and pairwise average nucleotide identity were used to find nearest neighbors, and Lyve-SET approximated a phylogeny. Eighteen of the isolates harbored the bont/B5 gene: of those, 17 were classified as sequence type ST36 and one was classified as ST104. A single isolate from Hawaii harbored bont/B1 and was determined to belong to ST110, and the isolate from California harbored bont/B1 and belonged to ST30. A tree constructed with Lyve-SET showed a high degree of homology among all the Hawaiian C. botulinum isolates that harbor the bont/B5 gene. Our results indicate that the bont/B-expressing isolates recovered from Hawaii are closely related to each other, suggesting local contamination of the drug paraphernalia or the wound itself with spores rather than contamination of the drug at manufacture or during transport. These findings may assist in identifying interventions to decrease wound botulism among persons who inject drugs.

A Rare Case of Botulism in an Adult Patient

Presentation of botulism in adults is extremely rare and symptoms can be easily confused for symptoms of acute stroke, Guillain-Barre, or myasthenia gravis. The purpose of this clinical case report is to ensure adult botulism will be included in the differential diagnoses for a patient with this presentation so swift and accurate care can be provided to ensure optimal patient outcome. A 41-year-old-female presented with complaints of sudden onset of difficulty speaking. The patient reports a history of intravenous polysubstance abuse and symptoms progressed to bilateral facial weakness, ptosis, and external ophthalmoplegia. With no notable findings from a non-contrast computed tomography and magnetic resonance imaging and given the symptoms, a diagnosis of wound botulism from intravenous drug use was made. Botulism antitoxin was given and the patient was admitted into the intensive care unit for supportive follow-up care. A colony of Clostridium species was discovered in this patient’s arm and the patient showed significant improvement after a few days of care.

CRISPR-Cas9-Based Toolkit for Clostridium botulinum Group II Spore and Sporulation Research

The spores of Clostridium botulinum Group II strains pose a significant threat to the safety of modern packaged foods due to the risk of their survival in pasteurization and their ability to germinate into neurotoxigenic cultures at refrigeration temperatures. Moreover, spores are the infectious agents in wound botulism, infant botulism, and intestinal toxemia in adults. The identification of factors that contribute to spore formation is, therefore, essential to the development of strategies to control related health risks. Accordingly, development of a straightforward and versatile gene manipulation tool and an efficient sporulation-promoting medium is pivotal. Our strategy was to employ CRISPR-Cas9 and homology-directed repair (HDR) to replace targeted genes with mutant alleles incorporating a unique 24-nt “bookmark” sequence that could act as a single guide RNA (sgRNA) target for Cas9. Following the generation of the sporulation mutant, the presence of the bookmark allowed rapid generation of a complemented strain, in which the mutant allele was replaced with a functional copy of the deleted gene using CRISPR-Cas9 and the requisite sgRNA. Then, we selected the most appropriate medium for sporulation studies in C. botulinum Group II strains by measuring the efficiency of spore formation in seven different media. The most effective medium was exploited to confirm the involvement of a candidate gene in the sporulation process. Using the devised sporulation medium, subsequent comparisons of the sporulation efficiency of the wild type (WT), mutant and “bookmark”-complemented strain allowed the assignment of any defective sporulation phenotype to the mutation made. As a strain generated by complementation with the WT gene in the original locus would be indistinguishable from the parental strain, the gene utilized in complementation studies was altered to contain a unique “watermark” through the introduction of silent nucleotide changes. The mutagenesis system and the devised sporulation medium provide a solid basis for gaining a deeper understanding of spore formation in C. botulinum, a prerequisite for the development of novel strategies for spore control and related food safety and public health risk management.

Wound Botulism in Black Tar Heroin Injecting Users: A Case Series

The incidence of wound botulism in injection drug users has increased since the introduction of black tar heroin. Many species of the Clostridium genus, most commonly Clostridium botulinum, Clostridium baratii, and Clostridium butyricum, have been associated with wound botulism. Patients often present with progressive bulbar weakness, including dysphagia, cranial nerve palsies, and loss of speech, in addition to symmetrical descending weakness of the upper extremities that may progress to the chest and lower extremities. In this article, we present 3 cases of wound botulism, in which the patients presented with bulbar weakness and were treated with botulism antitoxin heptavalent. The time to antitoxin administration and its effect on the patients’ clinical courses is compared.