Therapeutic indications and adverse reactions to intravenous gammaglobulin / Indicações terapêuticas e reações adversas da gamaglobulina intravenosa

The first therapeutic indication, and still currently the most applied of gamma globulin, is the one which uses its substitutive capacity in patients with antibodies deficiencies. Its immunomodulatory effectiveness with pro and anti-inflammatory activity holds a second place in their indications, in autoimmune and inflammatory illnesses. The first gamma globulin to be used in patients with agammaglobulinemia in the 50’s, were of intramuscular administration, with significant limitations on the volume and the infusion’samount, as well as being painful . For over 20 years intravenous immunoglobulin (IVIG) has been widely used in human pathology. The first proteolytic enzyme-treated intravenous immunoglobulins allowed large doses infusions, there by getting higher levels of IgC circulating in plasma, a subclass profile similar to the normal population, as well as a much higher average life expectancy. The pharmaceutical industry efforts brought about new more purified and viral safer immunoglobulins. The Cohn and cold ethanol methods were quickly supplemented with ulterior procedures that strengthened the viral safety of these products. The application of molecular techniques to the screening study of plasma donors, aswell as incorporating new viral inactivation procedures during its manufacture, have made of IVIG a safe product whose consumption has exponentially increased in recent years. IVIG’s high cost, the hypothetical plasma supply problems and risks associated to its administration made essential the writing of usage protocols for official agencies, which, besides, hospitals also adopted.

A primeira indicação terapêutica e, ainda hoje, a mais utilizada da gamaglobulina humana é aquela que usa a sua capacidade de substituição em pacientes com deficiências de anticorpos. Sua capacidade imunomoduladora, com atividades pro e anti-inflamatória, ocupam segundo lugar dentro de suas indicações, em doenças autoimunes e inflamatórias. As primeiras gamaglobulinas que foram utilizadas nos anos 50 em pacientes com agamaglobulinemia, tinham aplicação intramuscular, com limitações significativas relativas à dor, ao volume e a quantidade de infusão. Durante os últimos 20 anos, as imunoglobulinas intravenosas (IVIG) têm sido amplamente utilizadas em patologias humanas diversas. As primeiras IVIG tratadas por enzimas proteolíticas permitiram a infusão de grandes quantidades, obtendo assim níveis mais elevados de IgG sérica circulante, com um perfil de subclasses semelhante ao da população normal e uma vida média muito superior. O esforço da indústria farmacêutica fez com que aparecessem novas imunoglobulinas mais purificadas e com maior segurança contra infecções virais. Os métodos de Cohn e cold etanol foram rapidamente complementados com outros procedimentos que reforçavam a segurança antiviral desses produtos. A aplicação de técnicas moleculares para o estudo de rastreio do plasma dos doadores, bem como a incorporação de novos processos de inativação viral durante seu processo de fabricação, faz das IVIG um produto seguro cujo consumo tem aumentado exponencialmente nos últimos anos. O alto custo das IVIG, os hipotéticos problemas desde abastecimento de plasma e os riscos associados à sua administração tornaram essencial a redação de protocolos de uso para as agências oficiais que os hospitais também adotaram.

Proposta de implantação de centro de referência de imunobiológicos especiais (crie) em Feira de Santana, Bahia / Implementation of the proposed reference center for special immunobiological (crie) in Feira de Santana, Bahia / Propuesta de implantación del centro de referencia de inmunobiológicos especiales (crie) en Feira de Santana, Bahia

O Ministério da Saúde iniciou, em 1993, a implantação dos Centros de Referência de Imunobiológicos Especiais (CRIE) para facilitar o acesso de pessoas com quadros clínicos especiais a produtos de alto custo. Atualmente, existem mais de quarenta CRIE no Brasil, distribuídos em todas as capitais e em algumas cidades do interior. A proposta de implantação de um CRIE em Feira de Santana, Bahia, segunda cidade mais populosa do estado, sob a forma de um projeto de cooperação técnica entre a Universidade Estadual de Feira de Santana (UEFS) e a Secretaria de Saúde do Estado da Bahia (SESAB), envolvendo a Segunda Dires (SESAB) e o Hospital Geral Clériston Andrade (HGCA), objetiva beneficiar diretamente os portadores de quadros clínicos especiais, contribuir para aumentar as coberturas vacinais de crianças e adultos na rotina, acompanhar os casos de reações adversas aos imunobiológicos (vacinas e imunoglobulinas) e oportunizar aos estudantes de graduação e pós-graduação na área de Saúde a realização de projetos e trabalhos científicos, inserindo as estatísticas locais no contexto nacional. A publicação desta proposta poderá auxiliar outros profissionais na elaboração de projetos para implantação de CRIE em outras localidades.

In 1993 the National Health Service began the implementation of the Special Immunobiology Referral Centers (CRIE), in order to make it easier the access of people with special clinical needs to high cost drugs. Nowadays, in Brazil there are more than forty CRIEs, which are spread out in all the capitals and in some country towns. This new CRIE unit is a project of technical cooperation among the Universidade Estadual de Feira de Santana (UEFS) and Public Health Department of Bahia (SESAB), the II DIRES, Health Regional Directory which is subordinated to SESAB, and the General Hospital Cleriston Andrade (GHCA), a public hospital. The proposal for the implementation of one CRIE unit in Feira de Santana, the second most populous city of Bahia, aims to benefit immediately the carriers of special clinical needs, contributing to increase the coverage of vaccines in children and adults. It also aims to monitor the cases of adverse drugs reactions in the special immunobiologicals (vaccines and immunoglobulin), besides to give a chance to the Graduation and Post Graduation students in the Health Area to develop projects and academic works, inserting the local statistics in the national context. The publishing of this work will may help other professionals on the implementation of CRIE in other regions.

En 1993, el Ministerio de la Salud inició la implantación de los Centros de Referencia de Inmunobiológicos Especiales (CRIE), para facilitar el acceso de personas con cuadros clínicos especiales a productos de alto costo. Actualmente, existen más de cuarenta CRIE en Brasil, distribuidos en todas las capitales y en algunas ciudades del interior. La propuesta de implantación de un CRIE, dentro del proyecto de cooperación técnica entre la Universidad Estadual de Feira de Santana (UEFS) y la Secretaría de Salud del Estado de Bahia (SESAB), involucrando la Segunda Dires (SESAB) y el Hospital General Clériston Andrade (HGCA), en Feira de Santana, Bahía, segunda ciudad más poblada del estado de la Bahía, objetiva beneficiar directamente a los portadores de cuadros clínicos especiales, contribuir para aumentar las coberturas de vacunación de niños y adultos en la rutina, acompañar los casos de reacciones adversas a los inmunobiológicos (vacunas e inmunoglobulinas) y propiciar a los estudiantes de pregrado y posgrado en el área de Salud la realización de proyectos y trabajos científicos, insertando en el contexto nacional las estadísticas locales. La publicación de esta propuesta podrá auxiliar a 760 otros profesionales en la elaboración de proyectos para la implantación de los CRIE en otras localidades.

Is the skin sensitivity test required for administering equine rabies immunoglobulin.

Background. Rabies immunoglobulins are life-saving in patients with severe exposure to rabies. Despite the high degree of purification of equine rabies immunoglobulin (ERIG), the product inserts still recommend a skin sensitivity test before administration of this heterologous serum. A recent WHO recommendation states that there are no scientific grounds for performing a skin test before administering ERIG because testing does not predict reactions and it should be given irrespective of the result of the test. In this conflicting situation, we assessed the use of the skin sensitivity test in predicting adverse events to ERIG. Methods. The data analysed were from the Antirabies Clinic of the Kempegowda Institute of Medical Sciences Hospital, Bengaluru, India. The period of study was 26 months (June 2008–July 2010). The skin sensitivity test was validated by evaluating its sensitivity, specificity, predictability, falsepositive and false-negative results. Results. A total of 51 (2.6%) adverse events were reported in 31 (1.5%) subjects. Most of these were mild to moderate in nature and subsided without medication. There was no serious adverse event. The sensitivity and specificity of the skin sensitivity test to predict an adverse event was 41.9% and 73.9%, respectively. Conclusion. Our experience with the skin sensitivity test suggests that it may not be required before administering ERIGs, as recommended by WHO.

Imunoglobulinas no trato respiratório de bezerros sadios durante o primeiro mês de vida / Immunoglobulin in the respiratory tract of healthy calves during their first month of life

Estudou-se o perfil de variação das imunoglobulinas em lavados das regiões traqueobrônquica e broncoalveolar do trato respiratório de bezerros neonatos sadios. Vinte bezerros da raça Holandesa, recém-nascidos e clinicamente sadios, receberam o colostro e foram distribuídos em dois grupos de dez animais cada. O Grupo 1 foi submetido à técnica de sondagem nasotraqueal para obtenção de lavado bronco-alveolar (LBA) e o Grupo 2, à traqueocentese para colheita de lavado traqueobrônquico (LTB), sendo estes procedimentos realizados em intervalos semanais, iniciando-se nos primeiros dias pós-nascimento até, aproximadamente, um mês de vida. Verificaram-se maiores teores de IgG que IgA ao longo do trato respiratório e estas imunoglobulinas sofreram influências da região do trato respiratório lavado, bem como influência do tempo de vida dos bezerros. Pôde-se detectar maiores teores de imunoglobulinas no LTB, assim como as maiores taxas de IgM e IgA em comparação com aquelas do LBA. As imunoglobulinas do LBA tenderam a aumentar seus teores com a evolução das semanas de vida dos bezerros, enquanto tenderam a diminuir no LTB.

The immunoglobulin variation profile in lavages from the broncoalveolar and tracheo-bronchial regions of 20 healthy newborn Holstein male calves was studied. They were fed with colostrum and distributed into 2 groups, 10 animals each. Group 1 underwent the nasotracheal catheterization technique to get the bronchoalveolar lavage (BAL), and Group 2 underwent the tracheocenthesis to collect the tracheobronchial lavage (TBL), both procedures being carried out at a 7-day-interval, starting on the first days up to about one month of life. Higher IgG contents, as compared to IgA, were noted across the respiratory tract. These immunoglobulins were impacted by the site of the respiratory tract washed, as well as by the calves' life time in weeks. Higher immunoglobulin contents were detected in TBL, as well as higher IgM and IgA rates, as compared to BAL. The BAL immunoglobulins showed a tendency to be reduced in TBL.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeiräo Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of Säo Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeiräo Preto, University of Säo Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71 percent) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeiräo Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events

Vacinas e imunoglobulinas na gravidez / Vaccines and immunoglobulins during pregnancy

Os autores analisam alguns conceitos basicos sobre o uso de produtos imunobiologicos(vacinas e imunoglobulinas)na gestacao.Sao discutidas as principais situacoes de duvida,vivenciadas pelos obstertras,sobre o tema.Estes questionamentos surgem no momento em que uma gestante se expoe a individuo portador de uma infeccao potencialmente prevenivel ou atenuavel pelos imunobiologicos.Sao apresentadas as condutas consideradas adequadas para situacoes de exposicoes a rubeola,caxumba,varicela,hepatite B,tetano e outras.Mais do que uma revisao extensa sobre o tema,este texto pretende aser util como guia rapido de consulta para os que atuam em Servicos de Obstertricia

Uso clinico de imunoglobulinas / Clinical uses of immunoglobulins

Este artigo e resultado de revisao de literatura sobre o uso clinico de imunoglobulinas e tem como objetivo principal o de orientar e atualizar aqueles que utilizam essas preparacoes. Foram analisadas e discutidas as indicacoes profilaticas e terapeuticas desses compostos, as complicacoes e o risco de infeccoes associadas ao uso de imunoglobulinas.