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.

Botulinum toxin poisoning of food origin with neurological manifestations as the first symptom:A case report and differential diagnosis / 中风与神经疾病杂志

@#Botulinum toxin poisoning is a neuroparalytic disorder caused by botulinum toxin,mostly involving the presynaptic membrane of cranial nerves and peripheral neuromuscular junctions,manifesting as flaccid,symmetrical,descending paralysis. Due to the diverse clinical manifestations,it is easily confused with myasthenia gravis and Guillain-Barré syndrome in the absence of a clear history of suspected food consumption. We report a case of botulinum toxin poisoning characterized by fluctuating myasthenia gravis,bilateral ptosis,dysphagia,and double vision in our hospital. The patient denied a history of food or drug poisoning,had a positive fatigue test and a positive neostigmine test,and was initially diagnosed with myasthenia gravis. After treatment with pyridostigmine bromide,hormones,and immunosuppressants,there was no significant relief of symptoms. After detailed questioning,the patient recalled that his family members and friends had mild malaise and dizziness,which were initially overlooked. They had consumed the same homemade raw sauce from a jar at different times prior to the onset of the illness. Serological tests confirmed the diagnosis of botulinum toxin type A poisoning in the patient,as well as his family members and friends. Early diagnosis is key to the management of botulism poisoning. Patients presenting with fluctuating myasthenia,bilateral ptosis,dysphagia,and double vision should be questioned in detail about their history of consuming suspected food to rule out botulinum toxin poisoning,thereby avoiding misdiagnosis and delayed treatment.

Clinical characteristics among 67 cases of botulism in Xinjiang Uygur Autonomous Region, China / 中华神经科杂志

Objective:To investigate epidemiological and clinical characteristics of botulism, and the adverse events among those received botulinum antitoxin treatment.Methods:Patients with discharge diagnosis as botulism in the Second Affiliated Hospital of Xinjiang Medical University were enrolled between 2017 and 2021. The epidemiological and clinical characteristics were evaluated. Infection and mechanical ventilation as in-hospital outcomes according to baseline characteristics were analyzed. Patients with and without the interested outcomes were compared. The adverse outcomes among those received botulinum antitoxin treatment were investigated. Those with and without the adverse outcomes were also compared.Results:Sixty-seven cases of botulism were enrolled, and most cases got sick between January and March (32/67, 47.8%); among them 62 cases were Han ethnicity (92.5%); prevalence was highest in Aksu region (15/67, 22.4%); commonly seen symptoms and signs included fatigue (58/67, 86.6%), dysphagia (48/67, 71.6%), dizziness (42/67, 62.7%), ptosis (42/67, 62.7%), blurred vision (41/67, 61.2%), and limb weakness (35/67, 52.2%). Compared with patients without in-hospital infection ( n=52), patients with in-hospital infection ( n=15) were more likely to have severe botulism (0/52 vs 5/15, χ 2=19.79, P<0.001), diplopia (16/52, 30.8% vs 11/15, χ 2=8.77, P=0.003), dysarthria (17/52, 32.7% vs 11/15, χ 2=7.91, P=0.005), consciousness disorder (1/52, 1.9% vs 4/15, χ 2=10.32, P=0.008). Compared with patients without mechanical ventilation (62/67, 92.5%), patients with mechanical ventilation (5/67, 7.5%) were more likely to have severe botulism (5/5 vs 0/62, χ 2=41.17, P<0.001), and consciousness disorder (4/5 vs 1/62, 1.6%, χ 2=29.58, P<0.001). Among 67 cases of botulism, 19 cases (28.4%) had adverse events after receiving antitoxin treatment, with an average of 6.5 days from the antitoxin treatment beginning to the adverse event onset; among the 19 cases, 18 cases (94.7%) had rash. Age, sex, and severity did not differ between the groups with ( n=19) and without adverse events ( n=48) after receiving antitoxin treatment. Conclusions:Fatigue, dysphagia, dizziness, ptosis were the most frequent symptoms and signs in the botulism in Xinjiang Uygur Autonomous Region, China. Infection was a commonly seen complication of botulism, and proactive prevention and close monitoring were needed. Adverse events after receiving antitoxin were prevalent, and might not be associated with age, sex, and severity of botulism.

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.

Two cases of sporadic severe food-borne botulism / 中华全科医师杂志

Two female patients with acute onset of sporadic food-borne botulism are reported. Both patients presented cranial nerve palsy symptoms and rapidly involving respiratory muscles causing respiratory failure. The tracheal intubation, mechanical ventilation and active supportive measures were given at admission. The skull imaging and cerebrospinal fluid examination were negative, and the electromyography showed peripheral motor nerve damage. One patient was complicated with severe pneumonia. The botulinum toxin test was positive, and botulism poisoning was diagnosed. After early targeted treatment, patients were improved and discharged. Both patients had no complications and recurrence after discharge in 8 months of follow-up.

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.

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)

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)

Research advances in small molecule inhibitors of botulinum neurotoxins / 中国药理学与毒理学杂志

Botulinum neurotoxins (BoNTs) are the most deadly biological substances, including seven BoNT serotypes (A-G), and characterized by persistent flaccid paralysis of peripheral never terminals with high specificity called botulism. Due to their easy production and well-defined biological mechanism, BoNTs are wildly used in cosmetics and as very particular biopharmaceuticals in clinical therapy, so there is the risk of poisoning caused by accidental overdose. Also, because of their high toxicity, they are potential bioterrorism weapons. Thus, there is an urgent need for the development of BoNT inhibitors. In this review, based on the structure of BoNTs and the mechanism of botulism, we summarize recent advances in small molecule inhibitors targeting the Zn2+ active site of BoNT/A, such as 8-hydroxyquinoline and hydroxamic acid, or exosite of BoNT/A, small molecule inhibitors of BoNT/A through covalent binding that are irreversible, as well as small molecule inhibitors of targeting BoNT/B/ E light chain (LC).

Therapeutic effect of antitoxin on botulism type A: a preliminary observation of 8 cases / 中华整形外科杂志

Objective@#The study aimed to explore the recommended treatment for toxicosis of botulism toxin type A.@*Methods@#From January 2016 to August 2017, 8 patients with toxicosis of botulism toxin type A were hospitalized in Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine. All patients were female, 21-33 years of age, with an average age of 26.4 years. All patients showed progressive myasthenia and abnormal electromyography. The clinical manifestations and treatment outcomes of 8 patients in antitoxin group or non-antitoxin group were retrospectively analyzed. Five patients treated in plastic and reconstructive surgery department were included in the antitoxin group. They received skin test before injection, followed by intramuscular injection of 10 000-20 000 U antitoxins once a day for 2-3 days. Three patients treated in neurology department were included in the non-antitoxin group. They received only intravenous drip of neurotrophic drugs. After treatment, the improvement of clinical symptoms such as myasthenia and blepharoptosis was observed, and the electromyogram was followed up.@*Results@#The symptoms of myasthenia of the 5 patients in antitoxin treatment group were significantly improved, and the electromyogram signal returned to normal. However, for the 3 patients in non-antitoxin group, the symptoms of myasthenia did not significantly improve, and their electromyogram signal did not return to normal, even after 5 days′continuous treatment.@*Conclusions@#To regulate the cosmetic medical market is the key to prevent the accident of toxicosis of botulism toxin type A. It is necessary to make a definite diagnosis and medical intervene in time for the toxicosis. Antitoxin has a better curative effect, but further research is needed, to verify its safety and effectiveness.

Epidemiologia e fatores de riscos relacionados à intoxicação alimentar causada por Clostridium Botulinum: uma revisão narrativa / Epidemiology and risk factors related to food intoxication caused by Clostridium Botulinum: a narrative review

O botulismo é uma doença resultante da ação de uma toxina produzida pelo Clostridium botulinum. Devido à sua gravidade e alta mortalidade é considerado um problema de saúde pública. Nesta revisão apresentamos os principais fatores de riscos associados à intoxicação alimentar provocada pelo Clostridium botulinum, bem como realizamos um levantamento epidemiológico sobre o botulismo alimentar e infantil. A busca bibliográfica considerou as bases de dados Scielo, Medline, Lilacs e PubMed. Foram selecionados artigos originais e relatos de caso publicados em inglês, espanhol e português, incluindo publicações dos últimos dez anos. A partir das análises dos títulos, resumos e artigos, um total de 26 artigos foram incluídos nesta revisão. Verificou-se predomínio de 54% dos casos referentes ao botulismo alimentar, dos quais aproximadamente 58% confirmaram a ocorrência da toxina tipo A; e 35% referente ao botulismo infantil. Na literatura consultada os principais sintomas, relacionados ao botulismo alimentar, identificados foram: visão turva, vômito, paralisia flácida, náuseas, tontura, diplopia, dificuldade respiratória, disatria, disfagia, fraqueza muscular, boca seca, ptose e cefaleia. Dentre as principais fontes de contaminação, 65% das publicações selecionadas identificaram as conservas como principal causa do botulismo alimentar. Embora o mel (42%) seja a única fonte registrada de alimento veiculador do agente causador do botulismo infantil, alguns relatos na literatura (25%) associaram à doença com a inalação de poeira contendo esporos do Clostridium botulinum, bem como o uso de plantas medicinais (25%). Os sintomas mais comuns observados na literatura foram: constipação dificuldade respiratória e dificuldade de sucção. Apesar de vários relatos na literatura acerca das duas doenças, o botulismo ainda é muito subnotificado dado ao diagnóstico muitas vezes equivocado, ressaltando-se a importância do diagnóstico precoce no tratamento da doença pelos profissionais de saúde, bem como a disponibilidade de informações relevantes para a investigação epidemiológica de doenças de notificação compulsória. Os dados apresentados também demonstram a importância de sensibilizar a população dos principais riscos e medidas de prevenção, já que a maioria dos casos relatados está relacionada a práticas inadequadas de preparo dos alimentos. (AU)

Botulism is a disease resulting from the action of a toxin produced by Clostridium botulinum. Because of its severity and high mortality, it is considered a public health problem. In this review, we present the main risk factors associated with food poisoning caused by Clostridium botulinum, as well as an epidemiological survey on foodborne and infant botulism. A bibliographic search was conducted in SciELO, MEDLINE, LILACS and PubMed databases. Original articles and case reports published in English, Spanish and Portuguese in the past ten years were selected. After analyzing titles, abstracts and articles, 26 articles were used in this review. In total, 54% of the cases were related to foodborne botulism, of which approximately 58% had confirmed type A botulism, and 35% were related to infant botulism. In the literature consulted, the main symptoms related to foodborne botulism were blurred vision, vomiting, flaccid paralysis, nausea, dizziness, diplopia, respiratory distress, dysarthria, dysphagia, muscle weakness, dry mouth, ptosis and headache. Among the sources of contamination, 65% of the published studies reported home-canned foods as the main cause of foodborne botulism. Although honey (42%) is the only reported food source for the agent causing infant botulism, some reports in the literature (25%) associated the disease with inhalation of dust containing Clostridium botulinum spores, as well as use of medicinal plants (25%). The most common symptoms observed in the literature were constipation, difficulty breathing and difficulty suckling. Although several reports on the two forms of the disease exist, botulism remains under-reported because of often incorrect diagnosis. Thus, early diagnosis is important for an adequate treatment provided by health professionals, as well as availability of relevant information for the epidemiological investigation of notifiable diseases. The data presented in this study also demonstrate the importance of raising people's awareness to main risks and prevention measures, as most reported cases were related to inadequate food preparation practices. (AU)

Botulinum toxin A (BT-A) versus low-level laser therapy (LLLT) in chronic migraine treatment: a comparison / Toxina botulínica A (BT-A) versus laser terapia de baixa potência (LLLT) em enxaqueca crônica: Uma triagem comparativa

ABSTRACT The aim of this work was to evaluate patients with chronic migraine treated with botulinum toxin A (BT-A) and compare this with low level laser therapy (LLLT), referencing: pain days, pain intensity, intake of drugs/self-medication, anxiety and sleep disorders. Methods: Patients were randomized into two groups: BT-A group (n = 18) and LLLT group (n = 18). Each patient kept three pain diaries: one before (baseline) (30 days), one during treatment (30 days) and one after the post-treatment phase (30 days). Repeated ANOVA plus the Bonferroni post-test, Student's t test, and factorial analysis were applied, and p < 0.05 was accepted as significant. Results: Our data showed that both treatments were able to reduce headache days, acute medication intake and decrease the intensity of pain. Anxiety was reduced in the BT-A group, while sleep disturbance was reduced in the LLLT group. Conclusion: Our data showed that both treatments can be used to treat chronic migraine, without notable differences between them.

RESUMO O estudo comparou pacientes com cefaleia crônica (CM) tratados com toxina botulínica A (BT-A) versus terapia a laser de baixa intensidade (LLLT), relativos a: dias de dor, automedicação, nervosismo e distúrbios do sono. Métodos: Os pacientes foram randomizados em dois grupos: Grupo BT-A (n = 18) e Grupo LLLT (n = 18). Cada paciente preencheu três diários de dor, sendo um antes do início do tratamento (30 dias), durante o tratamento (30 dias) e um após tratamento (30 dias). ANOVA e pós-teste Bonferroni, teste T de Student e análise fatorial foram utilizados e valores de p < 0,05 foram considerados significativos. Resultados: Ambos os tratamentos foram capazes de reduzir os dias de dor e a ingestão aguda de medicação. Além disso, a ansiedade foi reduzida no grupo BT-A, enquanto que o distúrbio do sono foi reduzido no grupo LLLT. Conclusão: Nossos resultados mostraram que ambos os tratamentos são eficientes contra CM, sem diferença entre eles.

Economic impact of an outbreak of botulism in a cattle feedlot / Impacto econômico de um surto de botulismo em confinamento de bovinos

Botulism is a febrile disease, fatal in most cases, which affects the muscles of locomotion, chewing, and swallowing, as well as the diaphragm and intercostal muscles, causing flaccid paralysis and respiratory arrest. In bovines, the etiology is due to the ingestion of neurotoxins types C and D formed by the bacterium Clostridium botulinum in an animal or vegetal substance, during decomposition. Vaccination is one of the most effective prophylactic means to prevent this disease. In this study, an outbreak of botulism was evaluated in a feedlot with 6,300 finishing cattle, wherein 25 died as a consequence of contracting this disease. The economic losses resulting from the deaths were analyzed, and economic analysis was conducted, involving the estimated cost of vaccination for the whole herd under risk, with the objective of evaluating whether this prophylactic practice is a viable action plan. The financial loss due to the deaths resulting from botulism in the case studied was found to be R$55,560.00, equivalent to 0.39% of the total monetary value of the herd. The cost of immunizing the entire herd under risk was 14.06% (for toxins exclusive to toxins C and D) and 22.22% (for polyvalent vaccines against clostridiosis) of the financial loss incurred as a consequence of the recorded deaths. It was concluded that botulism is a disease that can cause a significant economic impact on intensive livestock production systems, and that vaccination is an economically viable prophylactic action if performed with adequate sanitary planning.(AU)

O botulismo é uma doença afebril, fatal na maioria dos casos, que afeta os músculos da locomoção, mastigação, deglutição e também o diafragma e os músculos intercostais, causando paralisia flácida e parada respiratória. Nos bovinos a etiologia é devido à ingestão de neurotoxinas tipos C e D previamente formadas pela bactéria Clostridium botulinum em matéria animal ou vegetal em decomposição. A vacinação é um dos meios profiláticos mais eficazes para prevenir esta doença. Neste trabalho, estudou-se um surto de botulismo em um confinamento com 6300 bovinos em terminação, no qual 25 morreram devido a esta doença. Foram analisadas as perdas econômicas em consequência das mortes, e por meio do percentual do prejuízo contabilizado, foi realizada uma análise econômica referente ao custo estimado da vacinação para todo do rebanho sob-risco com o objetivo de avaliar se esta prática profilática é um plano de ação viável. Como resultado, o prejuízo financeiro devido às mortes resultantes do botulismo no caso estudado foi de R$ 55.560,00 o equivalente a 0,39% do valor monetário total do rebanho. O custo da vacinação para imunizar todo o rebanho sob-risco foi equivalente a 14,06% (para vacinas exclusivas para toxinas C e D) e 22,22% (para vacinas polivalentes contra clostridioses) relativo ao prejuízo financeiro em consequência dos óbitos registrados. Concluiu-se que o botulismo é uma doença que pode provocar impacto econômico significativo em sistemas de corte intensivos em bovinos, e que, a vacinação é um meio profilático economicamente viável se for realizada por meio de um planejamento sanitário adequado.(AU)

Development of immunodetection system for botulinum neurotoxin serotype E

Background & objectives: Botulism, a potentially fatal paralytic illness, is caused by the botulinum neurotoxins (BoNTs) secreted by Clostridium botulinum. It is an obligate anaerobic, Gram-positive, spore-forming bacterium. BoNTs are classified into seven serotypes based on the serological properties. Among these seven serotypes, A, B, E and, rarely, F are responsible for human botulism. The present study was undertaken to develop an enzyme-linked immunosorbent assay (ELISA)-based detection system for the detection of BoNT/E. Methods: The synthetic gene coding the light chain of BoNT serotype E (BoNT/E LC) was constructed using the polymerase chain reaction primer overlapping method, cloned into pQE30UA vector and then transformed into Escherichia coli M15 host cells. Recombinant protein expression was optimized using different concentrations of isopropyl-?-D-1-thiogalactopyranoside (IPTG), different temperature and the rBoNT/E LC protein was purified in native conditions using affinity column chromatography. The purified recombinant protein was checked by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and further confirmed by western blot and matrix-assisted laser desorption ionization-tandem time-of-flight (MALDI-TOF). Polyclonal antibodies were generated against rBoNT/E LC using Freund's adjuvant in BALB/c mice and rabbit. Sandwich ELISA was optimized for the detection of rBoNT/E LC and native crude BoNT/E, and food matrix interference was tested. The developed antibodies were further evaluated for their specificity/cross-reactivity with BoNT serotypes and other bacterial toxins. Results: BoNT/E LC was successfully cloned, and the maximum expression was achieved in 16 h of post-induction using 0.5 mM IPTG concentration at 25癈. Polyclonal antibodies were generated in BALB/c mice and rabbit and the antibody titre was raised up to 128,000 after the 2nd booster dose. The developed polyclonal antibodies were highly specific and sensitive with a detection limit about 50 ng/ml for rBoNT/E LC and 2.5�[3] MLD50 of native crude BoNT/E at a dilution of 1:3000 of mouse (capturing) and rabbit (revealing) antibodies. Further, different liquid, semisolid and solid food matrices were tested, and rBoNT/E LC was detected in almost all food samples, but different levels of interference were detected in different food matrices. Interpretation & conclusions: There is no immune detection system available commercially in India to detect botulism. The developed system might be useful for the detection of botulinum toxin in food and clinical samples. Further work is in progress.

Surto de botulismo tipo C em equinos no Rio Grande do Sul / Outbreak of type C botulism in horses in Rio Grande do Sul

O botulismo nos animais domésticos é uma intoxicação fatal ocasionada pela ingestão da neurotoxina de Clostridium botulinum. Este trabalho descreve os aspectos epidemiológicos, clínicos e laboratoriais de um surto de botulismo tipo C em equinos de uma propriedade rural no município de Porto Alegre, Rio Grande do Sul. Do total de 20 equinos, sete (35%) foram acometidos e morreram, e um eutanasiado após apresentar prognóstico desfavorável. Os cavalos, criados extensivamente, apresentaram sinais clínicos semelhantes, caracterizados por dificuldade de locomoção, letargia, paralisia flácida progressiva, tremores musculares, sudorese, ataxia e quedas frequentes. Quatro equinos foram necropsiados e não apresentaram lesões macroscópicas e microscópicas significativas. Amostras de encéfalo e medula espinhal foram enviados para realização do exame de imunofluorescência direta e foram negativas para o vírus da raiva. Fragmentos de fígado dos quatro equinos necropsiados, amostras de sedimento do solo e água suspeita de dois açudes da propriedade foram avaliados pelo exame direto para a verificação da presença de toxina botulínica e/ou esporos de Clostridium botulinum. No bioensaio em camundongos e soroneutralização pode-se detectar toxina botulínica tipo C em uma amostra de fígado, ao passo que as amostras de sedimento do solo e água foram negativas em todos os ensaios. Com base nos dados epidemiológicos, clínicos e laboratoriais pode-se estabelecer o diagnóstico etiológico de botulismo causado pela toxina botulínica do tipo C, e sugere-se, a água estagnada dos açudes como aprovável fonte da toxina.(AU)

Botulism in domestic animals is a fatal poisoning caused by ingestion of Clostridium botulinum neurotoxin. This paper describes epidemiological, clinical and laboratorial aspects of a botulism type C outbreak in horses in a farm in Porto Alegre, Rio Grande do Sul. From a total of 20 horses, seven (35%) were affected and died, and one was euthanized after presenting poor prognosis. The horses, which were raised extensively, showed similar clinical signs, that included limited mobility, lethargy, progressive flaccid paralysis, muscle tremors, sweating, ataxia, and frequent falls. Four horses were necropsied and did not show significant macroscopic and microscopic lesions. Brain and spinal cord samples were analyzed by direct immunofluorescence and were negative for rabies. Liver fragments from the four necropsied horses, soil sediment samples, and suspect water from two reservoirs were evaluated by direct exam to verify the botulinum toxin and/or Clostridium botulinum spores presence. In the serum neutralization bioassay in mice, the type C botulinum toxin was detected in one liver sample, at the same time that the soil sediment and water samples were negative in all assays. Based on the epidemiological, clinical and laboratory data the etiological diagnosis of botulism was established by being caused by botulinum toxin type C, and it is suggested that the stagnant water of the dams is the likely source of the toxin.(AU)

Avaliação dos fatores físico-químicos que controlam o desenvolvimento do Clostridium botulinum em mortadelas comercializadas no estado do Rio de Janeiro / Evaluation of the physical-chemical factors that control the development of Clostridium botulinum in mortadella marketed in the state of Rio de Janeiro

A mortadela é um produto cárneo embutido muito consumido pelos brasileiros. Por ser um alimento embalado à vácuo apresenta condições propícias ao desenvolvimento de esporos bacterianos de patógenos como o Clostridium botulinum. Muitos aditivos usados na produção de carnes industrializadas visam melhorar o sabor, a cor e a aparência do produto, além de estender a sua vida útil. Desta forma, os fatores que garantem a segurança destes produtos são a conservação em baixas temperaturas após sua produção, na comercialização e no transporte; adição dos conservantes nitrato e nitrito de sódio nas concentrações adequadas; e o tratamento térmico adequado durante o seu processamento. Este trabalho teve como objetivo avaliar o risco da presença da toxina botulínica em amostras de mortadela através da análise das características físico químicas do produto. Foram coletadas, no varejo do município do Rio de Janeiro/RJ, dez amostras de mortadelas de cinco diferentes marcas comerciais, que foram analisadas quanto ao pH, atividade de água, teor de umidade, resíduo mineral fixo, temperatura de conservação, data de fabricação e prazo de validade. De acordo com o risco do crescimento do Clostridium botulinum, 100% das amostras apresentaram atividade de água (Aw) acima de 0,955 e pH acima dos valores de 4,5 o que favorece a multiplicação dessa bactéria.(AU)

Avaliação dos fatores físico-químicos que controlam o desenvolvimento do Clostridium botulinum em mortadelas comercializadas no estado do Rio de Janeiro

A mortadela é um produto cárneo embutido muito consumido pelos brasileiros. Por ser um alimento embalado à vácuo apresenta condições propícias ao desenvolvimento de esporos bacterianos de patógenos como o Clostridium botulinum. Muitos aditivos usados na produção de carnes industrializadas visam melhorar o sabor, a cor e a aparência do produto, além de estender a sua vida útil. Desta forma, os fatores que garantem a segurança destes produtos são a conservação em baixas temperaturas após sua produção, na comercialização e no transporte; adição dos conservantes nitrato e nitrito de sódio nas concentrações adequadas; e o tratamento térmico adequado durante o seu processamento. Este trabalho teve como objetivo avaliar o risco da presença da toxina botulínica em amostras de mortadela através da análise das características físico químicas do produto. Foram coletadas, no varejo do município do Rio de Janeiro/RJ, dez amostras de mortadelas de cinco diferentes marcas comerciais, que foram analisadas quanto ao pH, atividade de água, teor de umidade, resíduo mineral fixo, temperatura de conservação, data de fabricação e prazo de validade. De acordo com o risco do crescimento do Clostridium botulinum, 100% das amostras apresentaram atividade de água (Aw) acima de 0,955 e pH acima dos valores de 4,5 o que favorece a multiplicação dessa bactéria.

Mortadella is a sausage widely consumed in Brazil. It is a vacuum packed food, what provides conditions conducive to the development of spores of pathogen bacteria such as Clostridium botulinum. Many additives used in the production of processed meats aim to improve the flavor, color, appearance of the product and extend its shelf-life. The major factors to guarantee the safety of these products are low temperatures stocking, commercialization and transport; addition of preservatives sodium nitrate and sodium nitrite at the appropriate concentrations; and the appropriate heat treatment during processing. This work aimed to evaluate the risk of the presence of botulin toxin in mortadella samples by analyzing the physicochemical characteristics of the product. Ten mortadella samples from five different commercial brands were collected at a market, in the city of Rio de Janeiro, RJ, Brazil. The samples were analyzed for pH, water activity, moisture content, fixed mineral residue, storage temperature, date of manufacture and expiry date. According to the risk of Clostridium botulinum presence, all samples presented water activity (Aw) above 0.955 and pH above 4,5, conditions that favors bacteria proliferation.

Type C waterborne botulism outbreaks in buffaloes (Bubalus bubalis) in the Amazon region / Surtos de botulismo hídrico tipo C em búfalos (Bubalus bubalis) na região amazônica

Botulism is a poisoning caused by botulinum neurotoxins (BoNTs). BoNTs serotypes C and D are involved in botulism outbreaks in cattle in several countries. Despite the high number of buffaloes worldwide, the real impact of botulism in buffaloes is not known, because it is not a notifiable disease in Brazil and only few studies have evaluated the occurrence of the disease in buffaloes. Those studies did not conduct diagnostic tests to confirm the presence of BoNTs. The objective of the present study was to describe three outbreaks of botulism in buffaloes in the Brazilian Amazon region considering epidemiological and clinical data as well as laboratory diagnosis to confirm the presence of BoNTs. The results of the bioassay were negative in the tissues and in feed samples, but positive for BoNT C in water samples. Confirmation of the occurrence of botulism in buffaloes allows the implementation of preventive strategies in susceptible herds. Waterborne botulism in buffaloes is prevented by ensuring the constant circulation of water collections and restricting the presence of dead animals and bones in order to prevent the accumulation of organic matter and the development of anaerobic conditions, which might favor the replication of Clostridium botulinum. Another measure that can be adopted is the shading of the pasture, in order to maintain the thermal comfort for the buffaloes and to avoid the excess of permanence of them in the water pools.(AU)

Botulismo é uma intoxicação causada por neurotoxinas botulínicas (BoNTs). Os sorotipos C e D de BoNTs estão envolvidos em surtos de botulismo em bovídeos em vários países. Apesar do elevado número de búfalos em todo o mundo, o real impacto do botulismo em búfalos não é conhecido; pois não é uma doença de notificação obrigatória no Brasil e poucos estudos avaliaram a incidência desta doença em búfalos. Além disso, estes estudos não realizaram testes diagnósticos para confirmar a presença de BoNTs. O objetivo do presente estudo foi descrever três surtos de botulismo em búfalos na região amazônica brasileira, considerando dados epidemiológicos e clínicos, bem como o diagnóstico laboratorial para confirmar a presença de BoNTs. Os resultados do bioensaio em camundongos foram negativos em todos os tecidos e nas amostras de alimentos testados; no entanto foram positivos para BoNT C nas amostras de água. A confirmação da ocorrência de botulismo em búfalos permite a implementação de estratégias preventivas nos rebanhos. O botulismo hídrico nos búfalos pode ser prevenido assegurando-se que coleções de água fossem mantidas limpas, sem a presença de animais mortos e ossadas no seu interior e não permitindo o acúmulo de matéria orgânica e condições de anaerobiose favoráveis à multiplicação de Clostridium. botulinum. Outra medida que pode ser adotada é o sombreamento das pastagens, a fim de manter o conforto térmico dos búfalos e assim evitar o excesso de sua permanência dentro das fontes de água.(AU)