Botulismo del lactante: estudio descriptivo en una unidad de cuidados intensivos pediátricos / Infant botulism: a descriptive study in a pediatric intensive care unit

Introducción. El botulismo del lactante (BL) es la forma más frecuente de botulismo humano en Argentina. El objetivo es describir aspectos esenciales del diagnóstico y tratamiento de pacientes con BL internados en el servicio de terapia intensiva pediátrica (STIP). Métodos. Estudio observacional, descriptivo y retrospectivo. Se utilizó la base de datos del STIP con diagnóstico de BL en el período 2005-2020. Se registraron variables demográficas, métodos de diagnóstico, días de asistencia respiratoria mecánica convencional (ARMC), de ventilación no invasiva (VNI), estadía en STIP, mortalidad al alta hospitalaria. Resultados. Se registraron 21 pacientes con BL; 14 pacientes fueron varones, con una mediana de edad de 5 meses (RIC 2-6 m). El diagnóstico se realizó mediante técnica de bioensayo y se detectó la toxina en suero en 12 pacientes. Uno solo no requirió ARMC; 1 paciente fue traqueostomizado; 18 pacientes recibieron antibióticos; 5 recibieron VNI. Ningún paciente recibió antitoxina y no hubo fallecidos. La mediana de estadía hospitalaria fue 66 días (RI: 42-76); de internación en STIP, 48 días (RI: 29-78); y de ARMC, 37 días (RI: 26-64). La demora en la confirmación diagnóstica fue 15,8 ± 4,8 días. Conclusiones. La totalidad de los pacientes fueron diagnosticados con la técnica de bioensayo, que generó un tiempo de demora diagnóstica que excede los lapsos recomendados para la administración del tratamiento específico. Ningún paciente recibió tratamiento específico. El BL presentó baja mortalidad, pero tiempos de ARM e internación prolongados, que se asocian a infecciones sobreagregadas y uso frecuente de antibióticos.

Introduction. Infant botulism (IB) is the most common form of human botulism in Argentina. Our objective was to describe the main aspects of diagnosis and management of patients with IB admitted to the pediatric intensive care unit (PICU). Methods. Observational, descriptive, and retrospective study. The PICU database with IB diagnosis in 2005­2020 period was used. Demographic variables, diagnostic methods, days of conventional mechanical ventilation (CMV), non-invasive ventilation (NIV), length of stay in the PICU and mortality upon hospital discharge were recorded. Results. In total, 21 patients with IB were recorded; 14 were male, their median age was 5 months (IQR: 2­6 m). Diagnosis was made by bioassay, and the toxin was identified in the serum of 12 patients. Only 1 patient did not require CMV; 1 patient had a tracheostomy; 18 patients received antibiotics; 5 received NIV. No patient was administered antitoxin and no patient died. The median length of stay in the hospital was 66 days (IQR: 42­76); in the PICU, 48 days (IQR: 29­78); and the median use of CMV, 37 days (IQR: 26­64). The delay until diagnostic confirmation was 15.8 ± 4.8 days. Conclusions. All patients were diagnosed using the bioassay technique, which resulted in a diagnostic delay that exceeds the recommended period for the administration of a specific treatment. No patient received a specific treatment. IB was related to a low mortality, but also to prolonged use of MV and length of hospital stay, which were associated with cross infections and frequent antibiotic use.

Duration of Fecal Excretion of Clostridium Botulinum and Botulinum Neurotoxin in Patients Recovering from Infant Botulism.

This study sought to determine duration of fecal excretion of Clostridium botulinum organisms and neurotoxin after onset of infant botulism in 66 affected infants. Median excretion was longer for type A than type B patients (organisms: 5.9 vs 3.5 weeks, toxin: 4.8 vs 1.6 weeks, respectively). Toxin excretion always ceased before organism excretion. Antibiotic therapy did not affect duration of excretion.

Infant botulism: a descriptive study in a pediatric intensive care unit. / Botulismo del lactante: estudio descriptivo en una unidad de cuidados intensivos pediátricos.

Introduction. Infant botulism (IB) is the most common form of human botulism in Argentina. Our objective was to describe the main aspects of diagnosis and management of patients with IB admitted to the pediatric intensive care unit (PICU). Methods. Observational, descriptive, and retrospective study. The PICU database with IB diagnosis in 2005-2020 period was used. Demographic variables, diagnostic methods, days of conventional mechanical ventilation (CMV), non-invasive ventilation (NIV), length of stay in the PICU and mortality upon hospital discharge were recorded. Results. In total, 21 patients with IB were recorded; 14 were male, their median age was 5 months (IQR: 2-6 m). Diagnosis was made by bioassay, and the toxin was identified in the serum of 12 patients. Only 1 patient did not require CMV; 1 patient had a tracheostomy; 18 patients received antibiotics; 5 received NIV. No patient was administered antitoxin and no patient died. The median length of stay in the hospital was 66 days (IQR: 42-76); in the PICU, 48 days (IQR: 29-78); and the median use of CMV, 37 days (IQR: 26-64). The delay until diagnostic confirmation was 15.8 ± 4.8 days. Conclusions. All patients were diagnosed using the bioassay technique, which resulted in a diagnostic delay that exceeds the recommended period for the administration of a specific treatment. No patient received a specific treatment. IB was related to a low mortality, but also to prolonged use o  MV and length of hospital stay, which were associated with cross infections and frequent antibiotic use.

Introducción. El botulismo del lactante (BL) es la forma más frecuente de botulismo humano en Argentina. El objetivo es describir aspectos esenciales del diagnóstico y tratamiento de pacientes con BL internados en el servicio de terapia intensiva pediátrica (STIP). Métodos. Estudio observacional, descriptivo y retrospectivo. Se utilizó la base de datos del STIP con diagnóstico de BL en el período 2005-2020. Se registraron variables demográficas, métodos de diagnóstico, días de asistencia respiratoria mecánica convencional (ARMC), de ventilación no invasiva (VNI), estadía en STIP, mortalidad al alta hospitalaria. Resultados. Se registraron 21 pacientes con BL; 14 pacientes fueron varones, con una mediana de edad de 5 meses (RIC 2-6 m). El diagnóstico se realizó mediante técnica de bioensayo y se detectó la toxina en suero en 12 pacientes. Uno solo no requirió ARMC; 1 paciente fue traqueostomizado; 18 pacientes recibieron antibióticos; 5 recibieron VNI. Ningún paciente recibió antitoxina y no hubo fallecidos. La mediana de estadía hospitalaria fue 66 días (RI: 42-76); de internación en STIP, 48 días (RI: 29-78); y de ARMC, 37 días (RI: 26-64). La demora en la confirmación diagnóstica fue 15,8 ± 4,8 días. Conclusiones. La totalidad de los pacientes fueron diagnosticados con la técnica de bioensayo, que generó un tiempo de demora diagnóstica que excede los lapsos recomendados para la administración del tratamiento específico. Ningún paciente recibió tratamiento específico. El BL presentó baja mortalidad, pero tiempos de ARM e internación prolongados, que se asocian a infecciones sobreagregadas y uso frecuente de antibióticos.

Dual-Toxin ("Bivalent") Infant Botulism in California, 1976-2020: Epidemiologic, Clinical, and Laboratory Aspects.

OBJECTIVE: To assess the consequences of infant botulism that result from Clostridium botulinum strains that produce 2 botulinum toxin serotypes, termed "bivalent." STUDY DESIGN: Epidemiologic investigations used a standard questionnaire. Clostridium botulinum strains were isolated by standard methods. Botulinum neurotoxin (BoNT) serotypes and the relative amounts of toxins produced were identified using the standard mouse bioassay. BoNT subtypes and genomic locations were identified by DNA nucleotide sequencing. RESULTS: Thirty bivalent cases of infant botulism occurred in the 45 years (1976-2020), representing 2.0% of all California infant botulism cases, in the 3 geographic regions of southern California, the southern Central Valley, and mid-northern California. Toxin serotype combinations were Ba (n = 22), Bf (n = 7), and Ab (n = 1). More patients with illness caused by bivalent C botulinum Ba and Bf strains needed endotracheal intubation at hospital admission, 60.0% (18/30), than did patients with illness caused by monovalent BoNT/B strains, 34.3% (152/443). The Cbotulinum Ba and Bf strains produced BoNT/B5 and either BoNT/A4 or /F2. The Ab strain produced BoNT/A2 and /B1. All toxin gene clusters were on plasmids. CONCLUSIONS: Infant botulism caused by bivalent Cbotulinum strains occurs sporadically and in diverse locations in California. Affected patients with bivalent Ba and Bf strains lacked distinguishing epidemiological features but appeared to be more severely paralyzed at hospital presentation than patients with illness caused by only BoNT/B. These bivalent strains produced BoNT subtypes A2, A4, B1, B5, and F2, and all toxin gene clusters were on plasmids.

Botulism in the Brazilian Amazon: a life-threatening disease in a neglected population / Botulismo na Amazônia brasileira: uma doença fatal em uma população negligenciada

Abstract Background Botulism is a rare and potentially fatal neuroparalytic syndrome caused by the gram-positive anaerobe spore-forming bacteriumClostridium botulinum. The microorganism produces a neurotoxin that inhibits the presynaptic release of acetylcholine at the neuromuscular junction, clinically leading to a myasthenic syndrome. Objective To describe the recent outbreak of botulism cases and its demographic, clinical, and laboratory characteristics. Methods We report 4 patients with botulism in the recent outbreak occurred between 2017 and 2019 in the state of Amazon. Results Out of four patients with botulism, three contracted it from eating contaminated food and one had wound botulism. We emphasize the excellent clinical outcome of the different disease presentations in our case series. Conclusion The temporal proximity of these reports may suggest a new rise in the number of cases in the upcoming years. A possible hypothesis is that the rarity of the disease decreased the awareness regarding the primary prevention or even a diagnosis by an untrained physician.

Resumo Antecedentes O botulismo é uma síndrome neuroparalítica rara e potencialmente fatal causada pela bactéria anaeróbia gram-positiva formadora de esporosClostridium botulinum. O microrganismo produz uma neurotoxina que inibe a liberação pré-sináptica de acetilcolina na junção neuromuscular, levando clinicamente a uma síndrome miastênica. Objetivo Descrever o recente surto de casos de botulismo e suas características demográficas, clínicas e laboratoriais. Métodos Relatamos quatro pacientes com botulismo em surto recente ocorrido entre 2017 e 2019 no estado do Amazonas. Resultados Dos quatro pacientes com botulismo, três o contraíram devido ao consumo de alimento contaminado e um por ferimento. Enfatizamos o excelente resultado clínico das diferentes apresentações da doença em nossa série de casos. Conclusão A proximidade temporal dessas notificações pode sugerir um novo aumento no número de casos nos próximos anos. Uma possível hipótese é que a raridade da doença diminuiu a conscientização quanto à prevenção primária ou mesmo ao diagnóstico por médico destreinado.

Botulismo del lactante en Argentina. Trabajo multicéntrico / Infant botulism in Argentina. Multicentric work

Resumen El botulismo del lactante (BL), es la forma más frecuente del botulismo humano en la actualidad, es una enfermedad "rara" o "huérfana" ya que afecta a menos del 0,05 % de la población. El objetivo del presente trabajo es determinar la Incidencia del BL en la Argentina, evaluar el diagnóstico y tratamiento realizado, comparar la evolución y las secuelas al alta en pacientes con y sin tratamiento específico y, considerar las características climáticas (precipitaciones y vientos) y los estudios de muestras de suelos de las provincias con mayor cantidad de casos de BL. Presentamos un estudio multicéntrico, de cohorte (longitudinal) observacional, retrospectivo analizando las historias clínicas de los pacientes con BL, que ingresaron a Unidades de Cuidados Intensivos Pediátricos con asistencia respiratoria mecánica, desde el 1 de enero de 2010 hasta 31 de diciembre de 2013. Se consideró: edad, sexo, días previos al ingreso hasta diagnóstico por laboratorio, total internación en Unidades de Cuidados Intensivos Pediátricos con asistencia respiratoria mecánica, alimentación por sonda nasogástrica, tratamiento y secuelas. En Argentina entre 2010 al 2013 se registraron 216 casos de BL. En este trabajo se analizaron 79 pacientes provenientes de 11 provincias, que ingresaron a Unidades de Cuidados Intensivos Pediátricos. La edad promedio de los pacientes ingresados fue de 4 meses, de los cuales 90% recibía alimentación materna. Dieciocho pacientes de seis provincias recibieron antitoxina botulínica equina. El promedio de días de enfermedad previos al ingreso fue de 2 días en los pacientes que recibieron tratamiento con antitoxina botulínica equina y 4 días en los pacientes no tratados. Diagnóstico de laboratorio (Toxina A y Clostridium botulinum) a los 5 días en los tratados con antitoxina botulínica equina, y a los 11,5 en los no tratados. En los pacientes tratados con antitoxina botulínica equina, el promedio de días de internación fue de 30 versus 70 días en los no tratados (p=0,0001). El promedio días en las Unidades de Cuidados Intensivos Pediátricos de los pacientes tratados fue de 20 versus 54 días en los no tratados (p=0,0001). Los días de asistencia respiratoria mecánica en los tratados fue de 16 versus 43 días en los no tratados (p=0,0001) y los tratados requirieron 29 días de alimentación por sonda nasogástrica versus 70 días en los no tratados (p=0,0001). El 40% de los pacientes tratados presentaron neumonía asociada a respirador versus el 56% de los no tratados (p=0,0038), sepsis el 11% versus el 34% (p=0,005) y secuelas al alta 6% versus 64% (p=0,0001), respectivamente. En zonas con mayor número de casos, se observó una alta frecuencia de esporas en los suelos, asociado a clima seco y ventoso. Los resultados sugieren que el tratamiento precoz con antitoxina botulínica equina es una alternativa hasta disponer de inmuno-globulina botulínica humana. Los climas secos y ventosos favorecen la enfermedad.

Abstract Infant botulism (BL), the most common form of human botulism today, is a "rare" or "orphan" disease as it affects less than 0.05% of the population. The objective of this work is to determine the incidence of BL in Argentina. Evaluate the diagnosis and treatment performed. To compare evolution and sequelae at discharge in patients with and without specific treatment. Consider the climatic characteristics (precipitations and winds) and the studies of soil samples from the provinces with the highest number of BL cases. We present a retrospective, observational, multicenter, cohort (longitudinal) study analyzing the medical records of patients with BL, who were admitted to Pediatric Intensive Care Units with mechanical ventilation, from January 1,2010 to December 31,2013. The following were considered: age, sex, days prior to admission, until laboratory diagnosis, Pediatric Intensive Care Units, me-chanical respiratory assistance, average hospital days, nasogastric tube feeding, treatment and sequelae. In the country, 216 cases of BL were registered between 2010 and 2013. We analyzed 79 who were admitted to Pediatric Intensive Care Units from 11 provinces. Average age 4 months. Maternal nutrition 90%. Eighteen patients (6 provinces) received equine botulinum antitoxin .Mean days of illness prior to admission: 2 in those treated with equine botulinum antitoxin and 4 in those not treated. Laboratory diagnosis (Toxin A and Clostridium botulinum) at 5 days in treated with equine botulinum antitoxin, at 11.5 in untreated. Patients with equine botulinum antitoxin average hospital days 30 vs 70 in untreated patients (p=0.0001). Mean Pediatric Intensive Care Unit days 20 vs 54 (p=0.0001) of mechanical respiratory assistance 16 vs 43 (p=0.0001) and nasogastric tube feeding 29 vs 70 (p=0.0001). Those treated presented ventilator-associated pneumonia 40% vs 56% (p=0.0038) and sepsis 11% vs 34% (p=0.005). Sequelae at discharge 6% vs 64% (p=0.0001) in those not treated. In areas with a higher number of cases, high frequency of spores in soils, dry and windy weather. The results suggest that early treatment with equine botulinum antitoxin is an alternative until human botulinum immunoglobulin is available. The dry and windy climates favor the disease.

Botulismo del lactante grave por toxina tipo A y uso de antitoxina equina AB luego de 5 días de evolución, reporte de caso y revisión bibliográfica / Severe infant botulism due to type A toxin and use of equine AB antitoxin AB after 5 days of evolution, a case report and literature review

Resumen El botulismo del lactante (BL) es una enfermedad neuroparalítica potencialmente grave que afecta a niños menores de un año, ocasio nada por la ingesta y germinación de esporas de la bacteria del género Clostridium en tubo digestivo y la producción in situ de toxina botulínica (TB). Ésta se absorbe de manera intermitente y puede ser sostenida en el tiempo, condicionando una mayor exposición a la TB respecto a otras formas de botulismo. La TB representa el agente más letal conocido para el ser humano, con capacidad de producir parálisis flácida descendente, insuficiencia respiratoria y la muerte. Los lactantes representan la población más susceptible a esta toxiinfección. El eje central del manejo del BL radica en el diagnóstico precoz y tratamiento de sostén adecuado y oportuno. Si bien en la bibliografía consultada se describe que el tratamiento específico con antitoxina botulínica humana (BabyBIG® reduce el tiempo de hospitalización y estadía en Unidad de Cuidados Intensivos, la misma no se encuentra disponible en muchos países, incluida la Argentina. En nuestro país se encuentra disponible la antitoxina botulínica de origen equino (AtBE) bivalente A-B. La misma no posee indicación formal para el tratamiento del BL por la escasa experiencia en esta población, su corta vida media y los efectos adversos descritos, como son la sensibilización a antígenos equinos de por vida y posibles reacciones anafilácticas más graves en lactantes, basados en trabajos de la década de 1980 y opiniones de expertos. Se presenta el caso de una paciente de 5 meses asistida en el Hos pital de Niños "Superiora Sor María Ludovica" con BL severo, con requerimientos de asistencia ventilatoria mecánica y deterioro clínico durante la internación. Recibió AtBE a los 48 días de enfermedad, con respuesta favorable, a partir de una búsqueda bibliográfica sobre la eficacia y el perfil de seguridad de la AtBE en BL grave y la eficacia de su administración luego de 5 días de inicio del cuadro. A pesar de no haberse hallado bibliografía que avale la eficacia de la AtBE pasados 5 días de evolución, se plantea su uso en pacientes con BL grave e indicadores compatibles con presencia de TB en circulación, como la intensificación de la hipotonía muscular o la identificación de TB en materia fecal o suero. La búsqueda realizada arrojó datos sobre posibles beneficios de su uso, tanto antes como después de los 5 días de evolución del cuadro, y la ausencia de reportes de reacciones adversas severas en lactantes. Se concluye que el uso de la AtBE podría ser una opción terapéutica frente a la ausencia de BabyBIG® en pacientes con BL grave confirmado que requieran cuidados intensivos con soporte ventilatorio mecánico, frente a indicadores compatibles con TB circulante, independientemente del tiempo de evolución.

Abstract Infant botulism (BL) is a potentially serious neuroparalytic disease that affects children under one year old, caused by the ingestion and germination of spores of the Clostridium genus bacterium in the digestive tract and the in situ production of botulinum toxin (TB), which is absorbed intermittently and can be sustained over time, with longer exposure time to TB than other botulism forms. The TB represents the most lethal toxin known to humans and can cause descending flaccid paralysis, respiratory failure and death. Infants represent an especially susceptible population. Early diagnosis and supportive care are the cornerstone of BL management. Although specific treatment with human botulinum antitoxin (BabyBIG® has shown to reduce the hospitalization time and Intensive Care Unit stay in the consulted bibliography, it is not currently available in many countries, including Argentina. Botulinum antitoxin of equine origin (AtBE) bivalent A-B is available in our country. This antitoxin has not a formal indication in BL due to the limited experience of its use in this population, its short half-life and the adverse effects described, such as lifelong sensitization to equine antigens and possible more severe anaphylactic reactions in infants, based on studies from the 1980s and expert opinions. We present the case of a 5 month old patient assisted at the Children's Hospital "Superiora Sor María Ludovica" with severe BL, in need of mechanical ventilatory assistance and worsening of her clinical state during hospitalization, who received ATBE at 48 days of illness with a favorable response. A bibliographic search was carried out on the efficacy and safety profile of AtBE in severe BL and the efficacy of its administration after 5 days of illness onset. Even though bibliography on efficacy of ATBE after 5 days of evolution was not found, its use is proposed in patients with compatible indicators of circulating TB, such as worsening of muscular hypotonia or TB presence in feces or serum in severe ill patients. The carried out search has shown data of the possible benefits of its use, both before and after 5 days of disease onset, and the absence of severe adeverse reaction reports in infants. We concluded that the use of AtBE could be a therapeutic option in absence of BabyBIG® in patients with confirmed severe BL who require intensive care with mechanical ventilatory support and compatible indicators with circulating TB, regardless of the evolution time.

Comparative Genomics of Clostridium baratii Reveals Strain-Level Diversity in Toxin Abundance.

Clostridium baratii strains are rare opportunistic pathogens associated with botulism intoxication. They have been isolated from foods, soil and be carried asymptomatically or cause botulism outbreaks. Is not taxonomically related to Clostridium botulinum, but some strains are equipped with BoNT/F7 cluster. Despite their relationship with diseases, our knowledge regarding the genomic features and phylogenetic characteristics is limited. We analyzed the pangenome of C. baratii to understand the diversity and genomic features of this species. We compared existing genomes in public databases, metagenomes, and one newly sequenced strain isolated from an asymptomatic subject. The pangenome was open, indicating it comprises genetically diverse organisms. The core genome contained 28.49% of the total genes of the pangenome. Profiling virulence factors confirmed the presence of phospholipase C in some strains, a toxin capable of disrupting eukaryotic cell membranes. Furthermore, the genomic analysis indicated significant horizontal gene transfer (HGT) events as defined by the presence of prophage genomes. Seven strains were equipped with BoNT/F7 cluster. The active site was conserved in all strains, identifying a missing 7-aa region upstream of the active site in C. baratii genomes. This analysis could be important to advance our knowledge regarding opportunistic clostridia and better understand their contribution to disease.

Type C botulism outbreak in free-ranging waterfowl in Goiás / Surto de botulismo tipo C em aves aquáticas de vida livre em Goiás

Botulism is generally a fatal disease caused by ingestion of neurotoxins produced by Clostridium botulinum. The present study describes the epidemiological, clinical, and laboratory aspects of a type C botulism outbreak in free-living aquatic birds residing in an urban park in Quirinópolis, Goiás, Brazil. Among a population of approximately 80 waterfowl, a total of 30 birds, including ducks (Cairina moschata), teals (Anas platyrhynchos), and geese (Anser cygnoides), died within 10 days. Of these, six birds showed signs of flaccid paralysis of the pelvic limbs, eyelids, neck, and wings. To confirm the suspicion of botulism, four lake water samples, two samples of the feed consumed by the birds, and samples of serum, intestinal content, stomach content, and liver tissue from two teals that died after presenting clinical signs were analyzed. Using bioassay and neutralization with homologous antitoxin in mice, it was possible to detect the presence of botulinum toxin type C in a water sample and in the intestinal content of one of the necropsied teals. Additionally, the presence of C. botulinum type C was identified in the lake water using polymerase chain reaction. Based on the clinical signs and laboratory results, a diagnosis of botulism caused by botulinum toxin type C was confirmed with probable transmission by lake water.

O botulismo é uma doença geralmente fatal, causada pela ingestão de neurotoxinas produzidas pelo Clostridium botulinum. O presente estudo descreve os aspectos epidemiológicos, clínicos e laboratoriais de um surto de botulismo tipo C em aves aquáticas de vida livre habitantes de parque urbano em Quirinópolis, Goiás. De uma população de cerca de 80 aves aquáticas, um total de 30 aves, entre patos (Cairina moschata), marrecos (Anas platyrhynchos) e gansos (Anser cygnoides), morreram no intervalo de 10 dias. Destes, seis aves apresentaram sinais de paralisia flácida de membros pélvicos, pálpebras, pescoço e asas. Para confirmar a suspeita de botulismo, foram analisadas quatro amostras da água do lago, duas amostras da ração consumida pelas aves e amostras de soro, conteúdo intestinal, conteúdo estomacal e fígado de dois marrecos que morreram após apresentarem os sinais clínicos. Pelo bioensaio e neutralização com antitoxina homóloga em camundongos foi possível detectar a presença de toxina botulínica tipo C em uma amostra de água e no conteúdo intestinal de um dos marrecos necropsiados. Adicionalmente, pela reação em cadeia da polimerase identificou-se a presença de C. botulinum tipo C na água do lago. Com base nos sinais clínicos e resultados laboratoriais estabeleceu-se o diagnóstico de botulismo causado pela toxina botulínica tipo C e veiculada provavelmente pela água do lago.

Concurrent hospitalization of a married couple presenting with distinct symptoms but diagnosed with a life-threatening infectious disease

ABSTRACT We described the cases of a married couple hospitalized for distinct symptoms and developed a neuroparalytic syndrome with rapid progression. In Case 1, a 75-year-old woman was admitted for abdominal pain, diarrhea, and blurred vision. The patient developed acute respiratory failure, ptosis, and ophthalmoplegia. She died on day 15 because of an acute abdomen. In Case 2, her husband, a 71-year-old man, was admitted for diplopia. The patient developed abdominal distension and slurred speech. Later, he developed bilateral ptosis, ophthalmoparesis, and mydriasis. Botulism was suspected, and both patients received botulinum antitoxin. Our male patient survived but underwent prolonged rehabilitation.

The Role of the Pharmacist in the Treatment of Infantile Botulism.

Description Infantile botulism is a potentially devastating disease caused by ingestion of Clostridium botulinum spores through food products or dust particles. The toxin produced by the spores can lead to descending paralysis requiring hospitalization for supportive care which sometimes includes mechanical ventilation. Human Botulism Immune Globulin-Intravenous (BIG-IV or BabyBIG) from the Infant Botulism Treatment and Prevention Program (IBTPP) has been shown to greatly improve outcomes. A previously healthy 5-month-old infant was admitted to her regional hospital for poor feeding and lethargy. When the weakness progressed and she had trouble with protecting her airway, she was intubated and transferred to our institution. The primary diagnosis was infantile botulism and the decision was made to treat with BabyBIG. The pharmacy department was able to assist with obtaining BabyBIG, ensuring proper preparation, and coordinating the team for swift administration. In the days following the BabyBIG administration, the patient slowly started to recover her respiratory function and muscle tone. On day five of admission the patient was extubated. After transfer to the general pediatric floor the patient was given a transpyloric feeding tube and worked with gastrointestinal and nutrition services to improve oral feeding. She was discharged on day seventeen with plans to continue working with therapy and nutrition. BIG-IV can have a major impact in the recovery of infantile botulism. Pharmacists are in an optimal position to assist with coordinating the multidisciplinary team regarding its procurement, preparation, and administration.

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.

Analysis of a plasmid encoding botulinum neurotoxin type G gene in Clostridium argentinense.

Clostridium argentinense produces botulinum neurotoxin type G (BoNT/G). We sequenced and analyzed the plasmid harboring the bont/G gene, designated pCAG, in C. argentinense strain 2740. The pCAG consisted of 140,070 bp containing the bont/G gene cluster. Although this gene cluster showed high similarities in its DNA sequence and ORF arrangement to those of other bont gene clusters, the other regions of the plasmid did not. A phylogenetic study suggested that pCAG had a unique evolutionary history compared with other clostridial bont-harboring plasmids. This suggests that pCAG is possibly a novel type of plasmid expressing the bont/G gene in C. argentinense.

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Is botulism type C transmissible to human by consumption of contaminated poultry meat? Analysis of a suspect outbreak in French Guyana.

Botulism type C was suspected in a 46-year old man after consumption of sick poultry from a flock where botulism type C was confirmed. The patient developed characteristic signs of botulism, but investigation of biological samples did not confirm the presence of Clostridium botulinum or botulinum toxin. Despite having classical botulism symptoms, the man recovered very quickly. This raises the question of botulism transmission to humans by ingestion of contaminated poultry.

Jürgen Dõbereiner: a life dedicated to science / Jürgen Dõbereiner: uma vida dedicada à ciência

Dr. Jürgen Dõbereiner was born in Germany, on the 1st of November 1923, and lived in Brazil for 68 years during which time he developed a range of scientific projects in veterinary pathology and related disciplines. His main interests were the identification of new poisonous plants and mineral deficiencies and the causes of "cara inchada" ("swollen face" a periodontal disease) and botulism in livestock. This research has resulted in the improved health and saving of hundreds of thousands of animals, mainly cattle, annually, and is consequently of enormous economic value to the country. This contribution remains largely under appreciated. He was also involved in organizing diagnostic methods for identifying infectious diseases such as African swine fever and glanders in horses. One of his other major achievements has been the foundation and editing of specialized scientific journals for the documentation of veterinary science research results. At the beginning of his career in the 1950s, he and colleagues from the Institute for Animal Biology (IBA) were struggling to find a national scientific journal where research results from veterinary medicine could be published with practical application to the Brazilian reality. In consequence, the team founded "Arquivos do Instituto de Biologia Animal" and published three volumes (1959-1961). He then founded and edited "Pesquisa Agropecuária Brasileira" (The Brazilian Journal of Agricultural Research") that included a veterinary section. A series of veterinary volumes were published (1966-1976). Finally, in 1978 he helped create the Brazilian College of Veterinary Pathology (CBPA) that published "Pesquisa Veterinária Brasileira" (The Brazilian Journal of Veterinary Research) from 1981. The main goal was to communicate the most relevant disease problems of Brazilian livestock, in particular pathology and related subjects such as epidemiology, clinical study series and laboratory diagnosis to field veterinarians and academics. Dr. Jürgen Dõbereiner was president of CBPA (1978-2018) and chief editor of "Pesquisa Veterinária Brasileira" (1981-2018). He passed away on the 16th of October, 2018, at the age of 94 at his home in Seropédica/RJ, Brazil.(AU)

Dr. Jürgen Dõbereiner nasceu na Alemanha em 1 de novembro de 1923, durante 68 anos viveu no Brasil e desenvolveu trabalhos científicos no campo da patologia veterinária latu sensu. Sua contribuição científica de destaque foi em temas como plantas tóxicas de interesse pecuário, deficiências minerais em animais de produção, cara inchada (doença periodontal) dos ruminantes, botulismo e diagnóstico de doenças infecciosas. Estas pesquisas resultaram na melhoria da saúde e de centenas de milhares de animais, principalmente bovinos e, consequentemente, foram de enorme valor econômico para o país. Esta contribuição ainda permanece em grande parte subestimada. De grande destaque para a ciência brasileira foi ainda a sua atuação profissional na documentação científica de resultados de pesquisa. No início de sua carreira na década de 1950, Dr. Dõbereiner e outros pesquisadores do Instituto de Biologia Animal (IBA) detectaram a necessidade de um periódico científico nacional para publicar resultados de pesquisas com aplicação pratica à realidade brasileira. Dessa iniciativa surgiram os Arquivos do Instituto de Biologia Animal, que publicou três fascículos (1959-1961), em seguida o Dr. Jürgen Dõbereiner participou na fundação da revista Pesquisa Agropecuária Brasileira que publicou a Série Veterinária (1966-1976) e finalmente em 1978, houve a fundação do Colégio Brasileiro de Patologia Animal (CBPA) que publica desde 1981 a revista Pesquisa Veterinária Brasileira. Este periódico científico foi criado para apresentar à comunidade, principalmente veterinários de campo e professores, os principais problemas de saúde em animais de produção no Brasil, ou seja, patologia em seu sentido amplo, envolvendo as áreas de epidemiologia, clínica e diagnóstico laboratorial. Dr. Jürgen Dõbereiner, que foi presidente do CBPA (1978-2018) e Editor-Chefe da revista Pesquisa Veterinária Brasileira (1981-2018), faleceu em casa, em 16 de outubro de 2018, aos 94 anos, no município de Seropédica/RJ.(AU)

Jürgen Döbereiner: a life dedicated to science / Jürgen Döbereiner: uma vida dedicada à ciência

Dr. Jürgen Döbereiner was born in Germany, on the 1st of November 1923, and lived in Brazil for 68 years during which time he developed a range of scientific projects in veterinary pathology and related disciplines. His main interests were the identification of new poisonous plants and mineral deficiencies and the causes of "cara inchada" ("swollen face" a periodontal disease) and botulism in livestock. This research has resulted in the improved health and saving of hundreds of thousands of animals, mainly cattle, annually, and is consequently of enormous economic value to the country. This contribution remains largely under appreciated. He was also involved in organizing diagnostic methods for identifying infectious diseases such as African swine fever and glanders in horses. One of his other major achievements has been the foundation and editing of specialized scientific journals for the documentation of veterinary science research results. At the beginning of his career in the 1950s, he and colleagues from the Institute for Animal Biology (IBA) were struggling to find a national scientific journal where research results from veterinary medicine could be published with practical application to the Brazilian reality. In consequence, the team founded "Arquivos do Instituto de Biologia Animal" and published three volumes (1959-1961). He then founded and edited "Pesquisa Agropecuária Brasileira" (The Brazilian Journal of Agricultural Research") that included a veterinary section. A series of veterinary volumes were published (1966-1976). Finally, in 1978 he helped create the Brazilian College of Veterinary Pathology (CBPA) that published "Pesquisa Veterinária Brasileira" (The Brazilian Journal of Veterinary Research) from 1981. The main goal was to communicate the most relevant disease problems of Brazilian livestock, in particular pathology and related subjects such as epidemiology, clinical study series and laboratory diagnosis to field veterinarians and academics. Dr. Jürgen Döbereiner was president of CBPA (1978-2018) and chief editor of "Pesquisa Veterinária Brasileira" (1981-2018). He passed away on the 16th of October, 2018, at the age of 94 at his home in Seropédica/RJ, Brazil.(AU)

Dr. Jürgen Döbereiner nasceu na Alemanha em 1 de novembro de 1923, durante 68 anos viveu no Brasil e desenvolveu trabalhos científicos no campo da patologia veterinária latu sensu. Sua contribuição científica de destaque foi em temas como plantas tóxicas de interesse pecuário, deficiências minerais em animais de produção, cara inchada (doença periodontal) dos ruminantes, botulismo e diagnóstico de doenças infecciosas. Estas pesquisas resultaram na melhoria da saúde e de centenas de milhares de animais, principalmente bovinos e, consequentemente, foram de enorme valor econômico para o país. Esta contribuição ainda permanece em grande parte subestimada. De grande destaque para a ciência brasileira foi ainda a sua atuação profissional na documentação científica de resultados de pesquisa. No início de sua carreira na década de 1950, Dr. Döbereiner e outros pesquisadores do Instituto de Biologia Animal (IBA) detectaram a necessidade de um periódico científico nacional para publicar resultados de pesquisas com aplicação pratica à realidade brasileira. Dessa iniciativa surgiram os Arquivos do Instituto de Biologia Animal, que publicou três fascículos (1959-1961), em seguida o Dr. Jürgen Döbereiner participou na fundação da revista Pesquisa Agropecuária Brasileira que publicou a Série Veterinária (1966-1976) e finalmente em 1978, houve a fundação do Colégio Brasileiro de Patologia Animal (CBPA) que publica desde 1981 a revista Pesquisa Veterinária Brasileira. Este periódico científico foi criado para apresentar à comunidade, principalmente veterinários de campo e professores, os principais problemas de saúde em animais de produção no Brasil, ou seja, patologia em seu sentido amplo, envolvendo as áreas de epidemiologia, clínica e diagnóstico laboratorial. Dr. Jürgen Döbereiner, que foi presidente do CBPA (1978-2018) e Editor-Chefe da revista Pesquisa Veterinária Brasileira (1981-2018), faleceu em casa, em 16 de outubro de 2018, aos 94 anos, no município de Seropédica/RJ.(AU)

Type C botulism outbreak in feedlot cattle fed contaminated corn silage.

A large outbreak of botulism in feedlot steers fed corn silage contaminated with Clostridium botulinum neurotoxin type C (BoNT/C) is reported occurring in Midwestern Brazil in August 2017. The onset of the outbreak occurred 15 days after 1700 steers started to be fed the contaminated corn silage. Affected steers were alert and afebrile with varying degrees of flaccid paralysis in various muscle groups. A total of 1100 steers were affected, 1090 of which died within four days. Ten steers recovered after treatment with antitoxin. No gross or microscopic lesions were found in affected steers. The diagnosis was based on epidemiological data, characteristic clinical signs, and positive mouse bioassay results. This outbreak is interesting due to the high number of fatally affected cattle and the on-site diagnostic approach. This case report demonstrates the difficulties in diagnosing and treating botulism in cattle.