RESUMO
Combined vaccines for childhood are a strategy in the prevention of several diseases. These can maximize protection and decrease immunization schedules in children. New candidates are getting closer to being able to meet these needs, but they raise numerous strategic questions related to formulation and regulatory aspects. In addition to being immunogenic and protective must have low reactogenicity when combined with other antigens. Adjuvants are important components in achieving these combinations. Therefore, a reactogenicity study was designed for two Bordetella pertussis formulations containing hydroxide or aluminum phosphate in Sprague Dawley rats. Both formulations dose were administered in 0.2 mL intramuscularly. Clinical evaluations, body weight, water consumption, food, temperature, muscle volume, dermal irritability and pathological studies with special interest at the inoculation site were carried out. Only differences in body temperature and muscle volume were found with a slight increase in values with return to normal. The macroscopic study showed lesions at the site of inoculation, considered characteristics of aluminum adjuvants, such as granulomatous abscesses and the increase in regional lymph nodes near the inoculation site. As conclusion, there are no differences between the formulations of B. pertussis with hydroxide or aluminum phosphate resulted in low reactogenicity.
Las vacunas combinadas resultan una estrategia importante en la obtención de vacunas múltiples para la infancia y el uso de adyuvantes es un componente de gran valor en lograr estas combinaciones, además de ser inmunogénicas y protectoras deben tener baja reactogenicidad, cuando se combinan con diferentes antígenos. Por esta razón, se diseñó un estudio de reactogenicidad a dos formulaciones que contenían hidróxido y fosfato de aluminio con antígenos de Bordetella pertussis en ratas Sprague Dawley. Se administró a cada grupo de ensayo una dosis correspondiente de ambas formulaciones en 0,2 mL por vía intramuscular. Se realizaron observaciones clínicas, comportamiento del peso corporal, consumo de agua, alimentos, temperatura corporal, volumen muscular, irritabilidad dérmica y estudios anatomopatológicos macroscópicos, con especial interés en el sitio de inoculación. No se observaron síntomas, ni muertes en los animales durante el estudio. Tampoco se encontraron diferencias entre los grupos experimentales en cuanto al peso corporal, el consumo de agua y de alimentos; los estudios de temperatura corporal y volumetría muscular evidenciaron un ligero incremento en los valores, los cuales involucionaron rápidamente a la normalidad. En el estudio anatomopatológico macroscópico se observaron lesiones a nivel del punto de inoculación, consideradas propias de los adyuvantes que contienen aluminio, tales como formaciones abscedadas de tipo granulomatosas y el aumento de los ganglios linfáticos regionales cercanos al punto de inoculación. Se concluye que las formulaciones en hidróxido y fosfato de aluminio con antígenos de B.pertussis resultaron ser de baja reactogenicidad.
Assuntos
Animais , Ratos , Adjuvantes Farmacêuticos/efeitos adversos , Compostos de Alumínio/efeitos adversos , Reação no Local da Injeção , Vacina contra Coqueluche , Ratos Sprague-DawleyRESUMO
OBJECTIVES: The aims of this study were to describe clinical and laboratory manifestations of patients with levamisole-adulterated cocaine-induced vasculitis/vasculopathy and to propose a skin classification according to the distribution and severity of lesions. METHODS: We report the characteristics of 30 patients admitted with levamisole-adulterated cocaine-induced vasculitis/vasculopathy in 4 high-complexity institutions in Colombia, from December 2010 to May 2017. We compare our findings with the main published series. RESULTS: Median age was 31 years (interquartile range, 27-38 years) with a male-to-female ratio of 5:1. Eighty-three percent of the patients had retiform purpura affecting the limbs, buttocks, face, or abdomen; 73% had ear necrosis, 50% cutaneous ulcers, 17% genital necrosis, 13% oral ulcers, and 10% digital necrosis. Cutaneous involvement was classified according to the frequency of the compromised corporal area, and purpuric lesions were stratified in 4 grades of severity. Anti-neutrophil cytoplasmic autoantibodies were positive in 85% of the cases, lupus anticoagulant in 73%, and antinuclear autoantibodies in 57%; rheumatoid factor was negative in all cases. We found nephritis in 17 cases (57%). Prednisolone was used in most of the patients (70%), with other immunosuppressive agents being used in a lower percentage. Improvement was observed in 93% of the patients, but symptoms recurred in 40%, attributed to relapses in consumption. End-stage chronic renal disease developed in 10% of the cases, and 1 patient died. CONCLUSIONS: Because of rising cocaine consumption and levamisole adulteration frequency, levamisole-adulterated cocaine-induced vasculitis/vasculopathy is becoming more common. Detailed characterization of skin involvement coupled with multiple antibody positivity is essential for a diagnosis. Renal involvement is frequent, clinically and histologically heterogeneous, and potentially serious.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína , Glomerulonefrite , Levamisol , Púrpura , Vasculite , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/farmacologia , Adulto , Autoanticorpos/sangue , Cocaína/farmacologia , Colômbia , Inibidores da Captação de Dopamina/farmacologia , Contaminação de Medicamentos , Feminino , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Glomerulonefrite/terapia , Humanos , Levamisol/efeitos adversos , Levamisol/farmacologia , Masculino , Necrose , Administração dos Cuidados ao Paciente/métodos , Púrpura/induzido quimicamente , Púrpura/diagnóstico , Púrpura/imunologia , Púrpura/terapia , Pele/patologia , Resultado do Tratamento , Vasculite/induzido quimicamente , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/terapiaRESUMO
La aplicación de sustancias con fines estéticos de forma indiscriminada como aceites minerales, hidrocarburos, silicona industrial, entre otros, llevan a producir enfermedades en el organismo bien sea locales y/o sistémicas. La asociación entre el uso de estas sustancias y la aparición de enfermedades autoinmunes aún no está clara. No obstante, se han descrito series de pacientes con antecedentes de inyección por materiales de relleno con fines cosméticos, que posteriormente presentaron patologías autoinmunes como: la esclerosis sistémica, el lupus eritematoso sistémico, la artritis reumatoidea, el síndrome de Sjögren, fibromialgia y presencia aislada de algunos síntomas inespecíficos como artralgias, mialgias, deterioro cognitivo, malestar general y fiebre. La reacción inflamatoria excesiva que pueden desencadenar estas sustancias y sus graves consecuencias para el organismo y teniendo en cuenta el aumento de estas prácticas a nivel global, hace necesario concientizar que sólo a través de una adecuada educación a la comunidad y la preparación del personal de la salud, podrá combatirse el terrible daño que provocan en la población(1)
The application of substances with aesthetic purpose in an indiscriminate way as oils minerals, hydrocarbons, industrial silicon, and others, they take to produce illnesses well in the body it is local and/or systemic. The association between the use of these substances and the appearance of autoimmunity diseases is not still clear. Nevertheless cases series have been described patient with antecedent of injection for filler materials with cosmetics purpose that later presented defined autoimmunity such as systemic sclerosis, lupus, rheumatoid arthritis, Sjögren Syndrome, Fibromyalgia and the isolated presence of some symptoms nonspecific. The excessive inflammatory reaction that can cause these substances and their serious consequences for the organism, and keeping in mind the increase from these practices to global level is necessary to inform that alone through an appropriate education to the community and the preparation of the health professionals will be able to prevent and combat the terrible damage in the population(1)
Assuntos
Humanos , Artrite Reumatoide , Escleroderma Sistêmico , Autoimunidade , Biopolímeros/efeitos adversos , Adjuvantes Farmacêuticos/efeitos adversosRESUMO
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to previous exposure to an adjuvant substance. The clinical picture is very heterogeneous, from mild to severe manifestations, including death. However, the systematic analysis of severe ASIA cases has not been performed. The aim of this study was to systematically review the literature on severe ASIA cases. A systematic review of the literature was performed investigating severe ASIA cases. All publications were identified through PubMed, EMBASE, MEDLINE and Cochrane. Articles published from 2011 to 2016 were included. Severe ASIA was arbitrarily defined as follows: major organ involvement, life-threatening conditions, intensive treatment, disability, hospitalization and outcome (survival and death). Cases described before 2011 were excluded. From 2011 to 2016, we identified 4479 ASIA cases, of them 305 fulfilled arbitrary criteria of severe ASIA including our case presentation and 11 deaths. The majority of severe ASIA cases were related to HPV vaccine, silicone, influenza vaccine and mineral oil injections. The interval from exposition to severe manifestation was from 2 days to 23 years. (1) This is the first study that analyzes all cases published on ASIA with severe manifestations. (2) The current HPV vaccine is both effective and generally safe. However, it should be noted that severe autoimmune side effects have been reported in several studies. Severe ASIA may be observed after influenza vaccines, and other vaccines. (3) Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life-threatening of ASIA.
Assuntos
Adjuvantes Farmacêuticos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Humanos , SíndromeRESUMO
The emergence of autoimmunity after vaccination has been described in many case reports and series. Everyday there is more evidence that this relationship is more than casual. In humans, adjuvants can induce non-specific constitutional, musculoskeletal or neurological clinical manifestations and in certain cases can lead to the appearance or acceleration of an autoimmune disease in a subject with genetic susceptibility. The fact that vaccines and adjuvants can trigger a pathogenic autoimmune response is corroborated by animal models. The use of animal models has enabled the study of the effects of application of adjuvants in a homogeneous population with certain genetic backgrounds. In some cases, adjuvants may trigger generalized autoimmune response, resulting in multiple auto-antibodies, but sometimes they can reproduce human autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, autoimmune thyroiditis and antiphospholipid syndrome and may provide insights about the potential adverse effects of adjuvants. Likewise, they give information about the clinical, immunological and histologic characteristics of autoimmune diseases in many organs, especially secondary lymphoid tissue. Through the description of the physiopathological characteristics of autoimmune diseases reproduced in animal models, new treatment targets can be described and maybe in the future, we will be able to recognize some high-risk population in whom the avoidance of certain adjuvants can reduce the incidence of autoimmune diseases, which typically results in high morbidity and mortality in young people. Herein, we describe the main animal models that can reproduce human autoimmune diseases with emphasis in how they are similar to human conditions.
Assuntos
Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Farmacêuticos/efeitos adversos , Doenças Autoimunes/etiologia , Modelos Animais de Doenças , Vacinas/efeitos adversos , Animais , Autoimunidade , HumanosRESUMO
The term autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome refers to a wide group of immune-mediated diseases triggered by external agents. Several substances, such as vaccine adjuvants, squalene and silicone implants, are implied in the pathogenesis of ASIA syndrome. Treatment and prognosis of this complex condition are not completely known due to lack of good quality evidence. After a brief introductory literature review on ASIA, we report here two cases of patients that developed rapidly progressive systemic sclerosis clinical features after multiple intramuscular local injections of a substance recommended by a non-medical professional called ADE. ADE is an oily vitamin complex for veterinary use, and it was used in these cases for cosmetic muscular definition and enhancement purpose. To our knowledge, this is the first paper to describe the relation between injections of ADE and the development of ASIA with severe systemic sclerosis phenotype. Further investigation is needed to better understand the pathophysiology and to provide the basis for the treatment of this condition.
Assuntos
Adjuvantes Farmacêuticos/efeitos adversos , Esclerodermia Difusa/induzido quimicamente , Adjuvantes Farmacêuticos/administração & dosagem , Adulto , Humanos , Injeções Intramusculares , Masculino , Rituximab/uso terapêutico , Esclerodermia Difusa/tratamento farmacológico , Esclerodermia Difusa/patologia , Síndrome , Vitamina A/administração & dosagem , Vitamina D/administração & dosagem , Vitamina E/administração & dosagem , Vitaminas/administração & dosagemRESUMO
A traditional infectious disease vaccine is a preparation of live attenuated, inactivated or killed pathogen that stimulates immunity. Vaccine immunologic adjuvants are compounds incorporated into vaccines to enhance immunogenicity. Adjuvants have recently been implicated in the new syndrome named ASIA autoimmune/inflammatory syndrome induced by adjuvants. The objective describes the frequencies of post-vaccination clinical syndrome induced by adjuvants. We performed a cross-sectional study; adverse event following immunization was defined as any untoward medical occurrence that follows immunization 54 days prior to the event. Data on vaccinations and other risk factors were obtained from daily epidemiologic surveillance. Descriptive statistics were done using means and standard deviation, and odds ratio adjusted for potential confounding variables was calculated with SPSS 17 software. Forty-three out of 120 patients with moderate or severe manifestations following immunization were hospitalized from 2008 to 2011. All patients fulfilled at least 2 major and 1 minor criteria suggested by Shoenfeld and Agmon-Levin for ASIA diagnosis. The most frequent clinical findings were pyrexia 68%, arthralgias 47%, cutaneous disorders 33%, muscle weakness 16% and myalgias 14%. Three patients had diagnosis of Guillain-Barre syndrome, one patient had Adult-Still's disease 3 days after vaccination. A total of 76% of the events occurred in the first 3 days post-vaccination. Two patients with previous autoimmune disease showed severe adverse reactions with the reactivation of their illness. Minor local reactions were present in 49% of patients. Vaccines containing adjuvants may be associated with an increased risk of autoimmune/inflammatory adverse events following immunization.
Assuntos
Adjuvantes Farmacêuticos/efeitos adversos , Diabetes Mellitus Tipo 1/epidemiologia , Vacinas/efeitos adversos , Anormalidades Múltiplas/epidemiologia , Adjuvantes Farmacêuticos/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/epidemiologia , Autoimunidade/efeitos dos fármacos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Febre/epidemiologia , Seguimentos , Síndrome de Guillain-Barré/epidemiologia , Humanos , Incidência , Lactente , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Dermatopatias/epidemiologia , Síndrome , Vacinação/efeitos adversos , Vacinas/administração & dosagem , Adulto JovemRESUMO
Recently, reports have suggested grouping different autoimmune conditions that are triggered by external stimuli as a single syndrome called autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome is characterized by the appearance of myalgia, myositis, muscle weakness, arthralgia, arthritis, chronic fatigue, sleep disturbances, cognitive impairment and memory loss, and the possible emergence of a demyelinating autoimmune disease caused by systemic exposure after vaccines and adjuvants. In the current study, the authors reported the first Brazilian case of a woman who developed ASIA, which was characterized by arthralgia, changes in inflammatory markers, and chronic fatigue, after the pandemic anti-influenza A/H1N1 vaccine without causing any other rheumatic disease, and it had a positive outcome.