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.

Le blépharospasme post paralytique. À propos de 04 cas et revue de la littérature

Malgré sa bénignité, le blépharospasme post paralytique reste une affection pénible pour le patient du fait de ses répercussions multiples: fonctionnelles,psychologiques et sociales nécessitant ainsi une prise en charge multidisciplinaire. La méconnaissance des éléments de cette pathologie par les praticiens peut faire courir au patient des désagréments certains à cause de l'errance diagnostique et la prise en charge incomplète voire même inadéquate.L'idée mobilisatrice de ce travail est notre expériencesur le blépharospasme post paralytique dans le service de neurochirurgie du CHU de BAJAIA (Algérie) lorsque nous avons commencé à traiter chirurgicalement la paralysie faciale périphérique définitive par anastomose hypoglosso-faciale latéro-terminale en 2016. Nous avons opéré à ce jour 34 patients sur une cohorte de 150 patients qui ont présenté une paraly sie faciale périphérique toute étiologie confondue. Ce sont les patients non opérés car ayant déjà récupéré de leur paralysie, qui présentent au cours de la réha-bilitation de la fonction de leur nerf facial, un défaut derégénérescence occasionnant une dystonie faciale dont le Blépharospasme est l'une des manifestations les plus gênantes

Quality of horse F(ab')2 antitoxins and antirabies immunoglobulins: protein content and anticomplementary activity

Among other applications, immunotherapy is used for the post-exposure treatment and/or prophylaxis of important infectious diseases, such as botulism, diphtheria, tetanus and rabies. The effectiveness of serum therapy is widely proven, but improvements on the immunoglobulin purification process and on the quality control are necessary to reduce the amount of protein aggregates. These may trigger adverse reactions in patients by activating the complement system and inducing the generation of anaphylatoxins. Herein, we used immunochemical methods to predict the quality of horse F(ab′)2 anti-botulinum AB, anti-diphtheric, antitetanic and anti-rabies immunoglobulins, in terms of amount of proteins and protein aggregates. Methods Samples were submitted to protein quantification, SDS-PAGE, Western blot analysis and molecular exclusion chromatography. The anticomplementary activity was determined in vitro by detecting the production of C5a/C5a desArg, the most potent anaphylatoxin. Data were analyzed by one-way ANOVA followed by Tukey's post-test, and differences were considered statistically significant when p < 0.05. Results Horse F(ab′)2 antitoxins and anti-rabies immunoglobulin preparations presented different amounts of protein. SDS-PAGE and Western blot analyses revealed the presence of protein aggregates, non-immunoglobulin contaminants and, unexpectedly, IgG whole molecules in the samples, indicating the non-complete digestion of immunoglobulins. The chromatographic profiles of antitoxins and anti-rabies immunoglobulins allowed to estimate the percentage of contaminants and aggregates in the samples. Although protein aggregates were present, the samples were not able to induce the generation of C5a/C5a desArg in vitro, indicating that they probably contain acceptable levels of aggregates. Conclusions Anti-botulinum AB (bivalent), anti-diphtheric, antitetanic and anti-rabies horse F(ab′)2 immunoglobulins probably contain acceptable levels of aggregates, although other improvements on the preparations must be carried out. Protein profile analysis and in vitro anticomplementary activity of F(ab′)2 immunoglobulin preparations should be included as quality control steps, to ensure acceptable levels of aggregates, contaminants and whole IgG molecules on final products, reducing the chances of adverse reactions in patients.(AU)

Evidências de revisões sistemáticas Cochrane sobre uso da toxina botulínica / Evidence from systematic reviews Cochrane on use of botulinum toxin

Contexto: A toxina botulínica tem sido utilizada no tratamento de várias situações clínicas (de modo regulamentado ou não). Assim, é importante mapear a efetividade e a segurança de cada indicação, fornecendo evidências para a tomada de decisão. Objetivo: Mapear evidências de revisões sistemáticas Cochrane sobre o uso da toxina botulínica. Métodos: Revisão narrativa com busca sistematizada da literatura (overview) que incluiu revisões sistemáticas Cochrane. Resultados: Entre as 82 revisões sistemáticas da busca inicial, 24 preencheram os critérios de inclusão. As revisões sistemáticas concluíram que: (a) a toxina botulínica é eficaz para: bexiga hiperativa, dor no ombro, distonia cervical,lombalgia e ciatalgia, sialorreia na doença do neurônio motor/esclerose lateral amiotrófica, espasmos hemifaciais, esclerose múltipla, espasticidade de membros superiores na paralisia cerebral, blefaroespasmo; (b) as evidências atuais são insuficientes para apoiar o uso da toxina botulínica para: hipertrofia do masseter, dor miofascial, sialorreia na paralisia cerebral, disfonia espasmódica, estrabismo, disfunção de esfíncter esofágico superior e desordens neurológicas de deglutição; (c) há evidências de que a toxina botulínica não é eficaz para cervicalgia subaguda e crônica, pé cavo, espasticidade de membros inferiores na paralisia cerebral, acalasia primária, síndrome do desfiladeiro torácico e fissura anal. Conclusão: Nas situações clínicas para as quais há ensaios clínicos randomizados, eles possuem qualidade metodológica limitada, aumentando o risco de viés e reduzindo a confiança nos resultados. São necessários ensaios clínicos de qualidade para embasar o uso da toxina botulínica em situações clínicas nas quais ela já é utilizada, mesmo sem aprovação por órgão regulamentador nacional.

Effect of botulinum toxin type-A on traumatic spinal cord injury spasticity

To evaluate the effect of botulinum toxin type A on spasticity in spinal cord injured patients and their functional outcome. Forty spastic patients due to traumatic spinal cord injury were studied. Initial assessment included general and neurological examination, ASIA classification, motor power, spasticity grading and functional assessment at the start, at 3 and 6 months. All patients received conventional physiotherapy rehabilitation on daily basis for 3 months then three times weekly for another 3 months. Thirty patients [group I] received botulinum toxin type A in the spastic muscles, dose according to body weight. Ten patients [group II] did not receive botulinum toxin. There 'was no significant difference between groups I and II as regard ADL on the 3 assessments. FIM was significantly lower in group 2 at 3 and 6 months. Clonus score showed a significant higher score of grade 3 and 4 only at 6 months in group II. Spasm frequency scale showed a significant higher rate of scale 3 and 4 in group II at 3 and 6 months. Global pain scale showed no significant difference between groups I and II at any occasion. Adductor tone scale showed a significant higher rate of scale 3 and 4 in group II at 3 and 6 months. Modified Ashworth scale showed a significant higher rate of scale 3 and 4 in group II at 3 and 6 months. Botulinum toxin has a reducing effect on spasticity in spinal cord injured patients, consequently improving their functional outcome

Medical referral of patients with acute respiratory failure: lessons learned from a large outbreak of botulism in northern Thailand.

BACKGROUND: There was an outbreak of botulism in a district in Nan Province in upper northern Thailand. The outbreak occurred after the villagers took bamboo shoots preserved in a sealed bucket under anaerobic conditions (home-canned bamboo shoots). There were 209 people at risk, of whom 119 (56.9%) were hospitalized. Among the 119 cases, 42 (35.3%) needed ventilators. Of the 42 cases, 25 (59.5%) were transferred to another hospital. OBJECTIVE: Describe and review transferal processes of the 25 cases and document lessons learned for medical services response from a public health aspect. MATERIAL AND METHOD: Review of records and reports. RESULTS: All 25 cases were successfully transferred with no mishaps. The duration of transferal was less than 3 hours. CONCLUSION: Preparedness of local capacity to cope with botulism outbreak of this scale is important. However, it is also necessary to develop a good system for medical referral of severe cases, to be started early in the course of medical care.

survey on 80 cases of botulism and its clinical presentations as a public health concern

Botulism is a toxin-induced paralytic illness characterized by cranial nerve palsies and descending flaccid paralysis. Borulinum toxin is regarded as the most lethal ever-known substance. The diagnosis in sporadic cases and even in small outbreaks is the main physicians' challenge. The aim of this study was to assess clinical presentations of 80 cases of botulism referred to Loghman Hakim hospital in Tehran. A total of 80 botulism cases referred during a 10-year period [1996-2006] were included. The diagnosis of botulism was verified on epidemiological data and a clinical score of severity. Patients were assigned in 3 groups: mild, intermediate and severe. The study population included 40 males and 40 females with a mean age of 30.7 +/- 15.2 years [a range, 1-66 years]. The suspected causative foods were cheese in 25 [31%], and sea-food in 20 [25%]. The mean incubation period was 1.1 +/- 1.8 days [a range, 4 hours-10 days]. Nausea and vomiting was noted as the first symptom in 17 cases. Diagnosis was confirmed in 47 patients [58.8%]. The most common toxin subgroups were A [in 22 cases] and E [in 15 cases]. All the patients were treated with antitoxin and recovered without sequel, however, 6 patients were admitted to intensive care unit [ICU] and required ventilatory support. Only one patient [1.3%] died. The mainstays of therapy are meticulous intensive care [including mechanical ventilation, when necessary] and promptly treatment with antitoxin. Antitoxin should be given early in the course of illness, ideally <24 hours after onset of symptoms

Botulismo por herida en la provincia de Mendoza / Wound botulism in Mendoza

Se presenta una paciente con botulismo por herida, la forma menos frecuente del botulismo humano. Es la primera observación confirmada en Mendoza. Se trata de una paciente de sexo femenino, con el antecedente de herida punzante en rodilla derecha por una rama de árbol caída. Ingresó a terapia intensiva infantil con trastornos deglutorios, somnolencia y dificultad en la marcha. Presentaba además hipotonía generalizada, reflejo fotomotor lento, nistagmus y diplopía. Ante la sospecha de botulismo por herida, se envió material de la misma y sangre para estudio, detectándose en las dos muestras toxina botulímica tipo A. En el cultivo se aisló Clostridium botulinum tipo A. La evolución de la paciente, con el apoyo de asistencia respiratoria mecánica, antibiótico y antitoxina, fue al comienzo satisfactoria, pero falleció bruscamente a los 20 días del ingreso por una descompensación hemodinámica. Se hace una actualización del diagnóstico clínico y muy detalladamente del laboratorio; también algunas consideraciones sobre diagnóstico diferencial, tratamiento y prevención. El botulismo por herida debe sospecharse en aquellos pacientes que tengan factores de riesgo traumático o por abuso de drogas y que presenten trastornos simétricos de los pares craneales y debilidad muscular descendente

Diagnóstico bacteriológico de un caso de botulismo infantil y primer aislamiento de C. botulinum en Chile / Bacteriological diagnosis of an infant botulism case and first isolation of C. botulinum in Chile

En noviembre de 1994 se recibió, en el Laboratorio de Anaerobicos del Instituto de Salud Pública de Chile, una muestra de deposición de una lactante de dos meses de edad con el diagnóstico presuntivo de botulismo infantil. La muestra fus sembrada en los medios de cultivo correspondientes y en atmósfera anaerobia hasta obtener un cultivo puro. Este fue sometido a diferentes pruebas bioquímicas, las cuales fueron coincidentes con Clostridium botulinum grupo I. POsteriormente se procedió a confirmar el diagnóstico realizando el test de patogenicidad y neutralización en ratones CF-1. En base a los resultados observados se concluyó que la cepa aislada correspondía a clostridium botulinum grupo I tipo A, lo cual fue confirmado por el Centers for Disease Control de Atlanta. Este fue el primer aislamiento de C. botulinum a partir de una muestra clínica en Chile

Botulismo del lactante: formas clínicas graves, experiencia en Neuquén / Infant botulism: serious clinical forms experience in Neuquén

Se presentan nueve casos de botulismo del lactante (BL) internados en el Servicio de Pediatría del Hospital Provincial Neuquén durante el período abril 1985 marzo 1991: dos de ellos con severo compromiso del sistema nervioso autónomo, manifestado por midriasis paralítica bilateral, y otros tres sin la constipación previa habitual de observar en el ingreso. Los nueve niños tenían de dos a nueve meses de vida (X: 4,4 m), detectándose en seis de ellos toxina en sangre y heces y desarrollando en el coprocultivo de ocho pacientes Clostridum botulinum tipo A. Uno de los niños falleció y los restantes requirieron asistencia respiratoria mecánica por tiempo prolongado (X: 24,5 días). La mayoría de los casos se registró en primavera y verano (época de vientos moderados a intensos en ésta zona). El electromiograma fue útil para el diagnóstico en los ocho pacientes en que se realizó con "potenciales en escalera" en el 75 por ciento de los casos. Es probable que se registren más casos en ésta región de la Patagonia, y que algunos se presenten como síndromes de muerte súbita del lactante. Se analizan algunos aspectos epidemiológicos, cuadro clínico y tratamiento de ésta enfermedad, que debe ser bien conocida por todos los pediatras. Se rescata también la importancia del EMG en el diagnóstico

Botulismo: consideraçöes acerca de oito casos ocorridos no Triângulo Mineiro, Minas Gerais / Botulism: considerations about 8 cases ocurred in Triângulo Mineiro, Minas Gerais, Brazil

O botulismo constitui uma forma rara de intoxicaçäo alimentar, particularmente em nosso meio. A única epidemia comprovada desta doença no Brasil ocorreu na década de 1950, no Rio Grande do Sul, onde nove pessoas a adquiriram, após a ingestäo de conserva caseira de peixe. O presente estudo relata um surto de Botulismo Tipo A ocorrido em uma família de 8 membros, dos quais 7 contraíram esta toxinfecçäo após a ingestäo de carne suína conservada sob a forma de enlatado caseiro. Duas evoluiram para o óbito, e os restantes recuperaram-se após variável tempo de evoluçäo. Onze meses após, diagnósticou-se novo caso desta doença, cuja fonte da intoxicaçäo näo pôde ser detectada. Pretende-se com esta publicaçäo, divulgar a segunda epidemia comprovada de Botulismo no Brasil, e chamar atençäo para seu quadro clínico, diagnóstico e tratamento, praticamente desconhecidos em nosso meio

Botulismo / Botulism

Apresenta-se revisäo de literatura disponível sobre o botulismo, doença produzida pelas toxinas do C. botulinum, presentes como contaminantes de alimentos de preparo doméstico, semi-industrializados e mesmo industrializados ou produzidos no próprio intestino, em seguida à colonizaçäo pelo C. botulinum. A doença constitui problema médico-social em demanda de atençäo especial através do mundo, desde a documentaçäo por Van Emergen em 1987, de surto de botulismo acometendo 24 pessoas