Segurança da vacina contra febre amarela em imunodeprimidos: Revisão Sistemática e Metanálise
Segurança da vacina contra febre amarela em imunodeprimidos: Revisão Sistemática e Metanálise
Data
2021
Autores
Lagos, Letícia Wigg de Araújo
Journal Title
Journal ISSN
Volume Title
Publisher
Instituto Nacional de Cardiologia
Resumo
Introdução: A febre amarela é uma arbovirose, de curta duração e gravidade variável, incluindo formas graves, com alta mortalidade. Sem tratamento específico, a vacina é a medida mais eficaz para proteção contra a doença. A vacina contra febre amarela é composta de vírus vivo atenuado, sendo imunogênica e segura, contraindicada para imunodeprimidos. Eventos adversos não graves e graves são descritos em imunodeprimidos, mas estudos anteriores falharam em demonstrar essa associação. Objetivo: Avaliar o risco de eventos adversos, independente da gravidade, após a vacinação contra febre amarela em imunodeprimidos, quando comparado ao seu uso em indivíduos sem imunodepressão. Método: Foi conduzida uma revisão sistemática, com busca nas bases bibliográficas MEDLINE, LILACS, EMBASE, SCOPUS, DARE, Toxiline e Web of Science e literatura cinzenta. Foram selecionados ensaios clínicos randomizados, quasi-randomizados e não randomizados, estudos de coorte, caso controle, série de casos, relato de casos ou estudos transversais, que incluíssem participantes imunodeprimidos (indivíduos com infecção por HIV, submetidos a transplantes de órgãos, com neoplasia, doenças reumatológicas em uso de medicamentos imunodepressores e indivíduos em terapia imunodepressora por outras doenças) vacinados contra febre amarela. A seleção dos estudos e extração dos dados foi conduzida por dois revisores de forma independente. A qualidade metodológica dos estudos foi avaliada pelo ROBINS-I e a qualidade das evidências de acordo com o GRADE. Foi realizada análise descritiva e duas metanálises: de proporção e de fator de risco, identificando a medida sumária de risco relativo (RR) nos estudos que apresentavam variáveis adequadas para combinação. Foram avaliadas as bases de notificação de eventos adversos pós-vacinais EAPV-PNI e VAERS, com achados apresentados de maneira descritiva. O protocolo da revisão foi registrado no PROSPERO (CRD42020158807). Resultados: Foram recuperados 881 resultados, sendo incluídos 21 estudos. A maioria dos estudos incluídos apresentou risco crítico de viés na qualidade metodológica. Foram identificados, em uma série de casos, três casos de doença viscerotrópica associada a vacina de febre amarela seguida de óbito. Treze estudos apresentavam dados suficientes para a realização das metanálises propostas. Sete trabalhos, sem grupo comparador, tiveram seus resultados agregados na metanálise de proporção, identificando risco de 8,5% de imunodeprimidos apresentarem eventos adversos
após vacinação (IC 95% 0,07-21,8). Seis estudos de coorte apresentavam grupo comparador e foram combinados, com a medida sumária sinalizando para RR de 1,00 (IC 95% 0,78-1,29), não sendo provável que a utilização da vacina em indivíduos imunodeprimidos esteja associada a ocorrência de eventos adversos quando comparado ao uso em indivíduos não imunodeprimidos. Foi realizada análise de subgrupo, de acordo com a etiologia da imunodepressão. Em indivíduos com infecção por HIV, o RR foi 0,85 (IC 95% 0,53-1,38), e nas imunodepressões por outras causas, RR 1,11 (IC 95% 0,84-1,47), não sendo possível afirmar que imunodepressão de base aumenta o risco de eventos adversos pós-vacinais. As bases de notificação de eventos adversos pós-vacinais não apresentaram dados relacionados à imunodepressão. Conclusões: Não é possível afirmar que imunodeprimidos, independente da etiologia, apresentem maior risco de eventos adversos após a vacina contra febre amarela. São necessários estudos de qualidade metodológica superior e maior tamanho amostral.
Palavras-chave: Febre Amarela, Vacina contra Febre Amarela, Eventos Adversos, Revisão Sistemática, Imunodeprimido
Introduction: Yellow fever is an arbovirus, of short duration and variable severity, including severe forms, with high mortality. Without specific treatment, the vaccine is the most effective measure to protect against the disease. The yellow fever vaccine is composed of a live attenuated virus, being immunogenic and safe, contraindicated for immunocompromised patients. Non-serious and serious adverse events are described in immunocompromised individuals, but previous studies have failed to demonstrate this association. Objective: To evaluate the risk of adverse events, regardless of severity, after vaccination against yellow fever in immunocompromised individuals, when compared to its use in individuals without immunosuppression. Method: A systematic review was conducted, searching the bibliographic databases MEDLINE, LILACS, EMBASE, SCOPUS, DARE, Toxiline and Web of Science and gray literature. Randomized, quasi-randomized and non-randomized clinical trials, cohort studies, case-control, case series, case reports or cross-sectional studies were selected, including immunocompromised participants (individuals with HIV infection, undergoing organ transplants, with neoplasia, rheumatologic diseases in use of immunosuppressive drugs and individuals in immunosuppressive therapy for other diseases) vaccinated against yellow fever. Study selection and data extraction were conducted by two reviewers independently. The methodological quality of the studies was assessed by ROBINS-I and the quality of evidence according to GRADE. Descriptive analysis and two meta-analyses were performed: proportion and risk factor, identifying the summary measure of relative risk (RR) in studies that had variables suitable for combination. The bases for notification of post-vaccine adverse events EAPV-PNI and VAERS were evaluated, with findings presented in a descriptive manner. The review protocol was registered in PROSPERO (CRD42020158807). Results: 881 results were retrieved, including 21 studies. Most of the included studies had a critical risk of bias in methodological quality. In a series of cases, three cases of viscerotropic disease associated with yellow fever vaccine followed by death were identified. Thirteen studies had enough data to carry out the proposed meta-analyses. Seven studies, without a comparator group, had their results aggregated in the proportion meta-analysis, identifying an 8.5% risk of immunocompromised individuals presenting adverse events after vaccination (95% CI 0.07-21.8). Six cohort studies had a comparator group and were combined, with the summary measure signaling a RR of 1.00 (95% CI 0.78-1.29), it being unlikely that the use of the vaccine in immunocompromised individuals is associated with the occurrence of adverse events when compared to use in non-immunocompromised individuals. Subgroup analysis was performed according to the etiology of immunosuppression. In individuals with HIV infection, the RR was 0.85 (95% CI 0.53-1.38), and in immunosuppression from other causes, RR 1.11 (95% CI 0.84-1.47), it is not possible to state that underlying immunosuppression increases the risk of adverse post-vaccination events. The reporting databases of adverse post-vaccination events did not present data related to immunosuppression. Conclusions: It is not possible to state that immunocompromised individuals, regardless of etiology, have a higher risk of adverse events after yellow fever vaccine. Higher methodological quality studies and larger sample sizes are needed. Keywords: Yellow Fever, Yellow Fever Vaccine, Adverse Events, Systematic Review, Immunodepressed
Introduction: Yellow fever is an arbovirus, of short duration and variable severity, including severe forms, with high mortality. Without specific treatment, the vaccine is the most effective measure to protect against the disease. The yellow fever vaccine is composed of a live attenuated virus, being immunogenic and safe, contraindicated for immunocompromised patients. Non-serious and serious adverse events are described in immunocompromised individuals, but previous studies have failed to demonstrate this association. Objective: To evaluate the risk of adverse events, regardless of severity, after vaccination against yellow fever in immunocompromised individuals, when compared to its use in individuals without immunosuppression. Method: A systematic review was conducted, searching the bibliographic databases MEDLINE, LILACS, EMBASE, SCOPUS, DARE, Toxiline and Web of Science and gray literature. Randomized, quasi-randomized and non-randomized clinical trials, cohort studies, case-control, case series, case reports or cross-sectional studies were selected, including immunocompromised participants (individuals with HIV infection, undergoing organ transplants, with neoplasia, rheumatologic diseases in use of immunosuppressive drugs and individuals in immunosuppressive therapy for other diseases) vaccinated against yellow fever. Study selection and data extraction were conducted by two reviewers independently. The methodological quality of the studies was assessed by ROBINS-I and the quality of evidence according to GRADE. Descriptive analysis and two meta-analyses were performed: proportion and risk factor, identifying the summary measure of relative risk (RR) in studies that had variables suitable for combination. The bases for notification of post-vaccine adverse events EAPV-PNI and VAERS were evaluated, with findings presented in a descriptive manner. The review protocol was registered in PROSPERO (CRD42020158807). Results: 881 results were retrieved, including 21 studies. Most of the included studies had a critical risk of bias in methodological quality. In a series of cases, three cases of viscerotropic disease associated with yellow fever vaccine followed by death were identified. Thirteen studies had enough data to carry out the proposed meta-analyses. Seven studies, without a comparator group, had their results aggregated in the proportion meta-analysis, identifying an 8.5% risk of immunocompromised individuals presenting adverse events after vaccination (95% CI 0.07-21.8). Six cohort studies had a comparator group and were combined, with the summary measure signaling a RR of 1.00 (95% CI 0.78-1.29), it being unlikely that the use of the vaccine in immunocompromised individuals is associated with the occurrence of adverse events when compared to use in non-immunocompromised individuals. Subgroup analysis was performed according to the etiology of immunosuppression. In individuals with HIV infection, the RR was 0.85 (95% CI 0.53-1.38), and in immunosuppression from other causes, RR 1.11 (95% CI 0.84-1.47), it is not possible to state that underlying immunosuppression increases the risk of adverse post-vaccination events. The reporting databases of adverse post-vaccination events did not present data related to immunosuppression. Conclusions: It is not possible to state that immunocompromised individuals, regardless of etiology, have a higher risk of adverse events after yellow fever vaccine. Higher methodological quality studies and larger sample sizes are needed. Keywords: Yellow Fever, Yellow Fever Vaccine, Adverse Events, Systematic Review, Immunodepressed
Description
Palavras-chave
Febre Amarela, Vacina contra Febre Amarela, Eventos Adversos, Revisão Sistemática, Imunodeprimido, Yellow Fever, Yellow Fever Vaccine, Adverse Events,, Systematic Review, Immunodepressed
Citação
Lagos LWA. Segurança da vacina contra febre amarela em imunodeprimidos: Revisão Sistemática e Metanálise. Rio de Janeiro. Dissertação [Mestrado Profissional em Avaliação de Tecnologias em Saúde] Instituto Nacional de Cardiologia - INC; 2021.