Evidence syntheses to support decision-making related to the Covid-19 pandemic.

The COVID-19 pandemic generated a large volume of scientific productions with different quality levels. The speed with which knowledge was produced and shared worldwide imposed on health management the challenge of seeking ways to identify the best available evidence to support its decisions. In response to this challenge, the Department of Science and Technology of the Brazilian Ministry of Health started offering a service to produce and provide scientific knowledge addressing priority public health issues in the pandemic scenario. Drug treatments, non-pharmacological measures, testing, reinfection and immunological response, immunization, pathophysiology, post-COVID syndrome and adverse events are among the topics covered. In this article, we discuss the strengths and lessons learned, as well as the challenges and perspectives that present a real example of how to offer the best scientific evidence in a timely manner in order to assist the decision-making process during a public health emergency.

An evidence-informed policymaking (EIPM) competency profile for the Brazilian Health System developed through consensus: process and outcomes.

BACKGROUND: Evidence-informed policymaking (EIPM) requires a set of individual and organizational knowledge, skills and attitudes that should be articulated with background factors and needs. In this regard, the development of an EIPM competency profile is important to support the diagnosis, planning and implementation of EIPM. PURPOSE: To present the process and outcomes of the development of an EIPM competency profile by an expert committee, to be applied in different contexts of the Brazilian Health System. METHODS: A committee of experts in EIPM shared different views, experiences and opinions to develop an EIPM competency profile for Brazil. In six consensus workshops mediated by facilitators, the committee defined from macro problems to key actions and performances essential for the competency profile. The development steps consisted of: (1) Constitution of the committee, including researchers, professionals with practical experience, managers, and educators; (2) Development of a rapid review on EIPM competency profiles; (3) Agreement on commitments and responsibilities in the processes; (4) Identification and definition of macro problems relating to the scope of the competency profile; and (5) Outlining of general and specific capacities, to be incorporated into the competency profile, categorized by key actions. RESULTS: The development of the EIPM competency profile was guided by the following macro problems: (1) lack of systematic and transparent decision-making processes in health policy management; (2) underdeveloped institutional capacity for knowledge management and translation; and (3) incipient use of scientific evidence in the formulation and implementation of health policies. A general framework of key actions and performances of the EIPM Competency Profile for Brazil was developed, including 42 specific and general key actions distributed by area of activity (Health Management, Scientific Research, Civil Society, Knowledge Translation, and Cross-sectional areas). CONCLUSIONS: The competency profile presented in this article can be used in different contexts as a key tool for the institutionalization of EIPM.

Incidence of Guillain-Barré syndrome in the world between 1985 and 2020: A systematic review.

Introduction: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy that affects the peripheral nervous system. The study aimed to describe the incidence of GBS in the world up to the year 2020. Methods: A systematic review was conducted. Searches were done in four databases, PUBMED, EMBASE, EBSCO and Biblioteca virtual em Saude (BVS), and in grey literature and manual search in the reference lists of eligible studies. Results: A total of 72 studies were included. The incidence of GBS among the cohort studies varied from 0.30 to 6.08 cases per 100.000 habitants and 0.42 to 6.58 cases per 100.000 person-years. Among the self-controlled studies, the risk incidence ranged from 0.072 to 1 case per 100.000 habitants and 1.73 to 4.30 cases per 100.000 person-years. Conclusions: The reported incidence of GBS in the world among the studies included in the review is slightly higher than that reported in previous studies. The highest incidence rates were associated with public health events of international concern.

Perfil de competência do profissional em PIE no Brasil: relatório / Projeto ESPIE / Professional competency profile in PIE in Brazil: report / ESPIE Project

O projeto Apoio à Formulação e Implementação de Políticas Públicas de Saúde Informadas por Evidências (ESPIE) é desenvolvido pelo Instituto Sírio-Libanês de Ensino e Pesquisa do Hospital Sírio-Libanês (IEP/HSL), no âmbito do Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS), em parceria com o Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos do Ministério da Saúde (DECIT/SCTIE/MS). O projeto ESPIE desenvolveu o Perfil de Competência do Profissional de PIE para o Brasil, com o objetivo de subsidiar atividades educacionais relacionadas com Políticas Informadas por Evidências (PIE), mas também apoiar o planejamento e ações de diferentes organizações no contexto da gestão da saúde no Sistema Único de Saúde (SUS). O perfil de competência foi desenvolvido e validado por um grupo de autoria constituído por técnicos das instituições envolvidas e especialistas convidados. O objetivo de criação do grupo de autoria foi agregar diferentes visões, experiências e opiniões ao processo de construção do perfil de competência em PIE. O grupo de autoria discutiu e definiu, ao longo de seis oficinas realizadas no ano de 2021, desde os macroproblemas até as ações-chave e desempenhos considerados essenciais. O processo de elaboração deste perfil foi orientado pelos seguintes macroproblemas: 1) processos decisórios na gestão das políticas de saúde pouco sistemáticos e transparentes; 2) capacidade institucional para gestão e tradução do conhecimento pouco desenvolvida e 3) incipiente incorporação das evidências científicas ao processo de formulação e implementação de políticas de saúde. Este documento consiste um meta-ponto de vista sobre o perfil de competência do profissional de PIE no Brasil e está endereçado aos macroproblemas no âmbito do SUS e inclui ações-chave e desempenhos que compõem um conjunto de conhecimentos, habilidades e atitudes, necessário para uma atuação institucional competente em PIE.

An accuracy study of the clinical diagnosis of periodontitis in pregnant women.

BACKGROUND: There exists a diverse range of criteria used in epidemiological studies for the diagnosis of periodontitis. The results from these studies should be evaluated with consideration to the diagnostic criteria used, and this may account for differences between studies especially in some population groups such as pregnant females. The objective is to evaluate the diagnostic criteria used in a variety of epidemiologic studies of periodontitis in pregnant females. METHODS: An accuracy study with cross-sectional design was performed out from a database of 671 pregnant females, using six different sets of criteria for the diagnosis of periodontitis. Women were classified for periodontitis, as follows: Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP, 2012 criterion), the gold standard, Gomes-Filho et al.(2018) criterion, Albandar et al.(2007) criterion, Bassani et al.(2007) criterion, López et al.(2002) criterion, and Nesse et al.(2008) criterion. For comparison amongst the gold standard and the other criteria, sensitivity, specificity, predictive values, and likelihood ratio were determined. RESULTS: The frequency of periodontitis ranged from 25.0% to 90.2%. The Bassani et al. (2007) criterion was found to be more sensitive among the studies, and thus more suitable for diagnostic screening studies. Gomes-Filho et al.(2018), Albandar et al. (2007), López et al. (2002), and Nesse et al. (2008) criteria were considered more specific, which makes them more useful for studies of periodontitis with the aim of using diagnosis for confirmation of disease. CONCLUSIONS: A variation in the occurrence of periodontitis was observed. The criterion must be chosen according to the research aims and population characteristics.

Pharmacological therapies for patients with human coronavirus infections: a rapid systematic review. / Terapia medicamentosa para infecções por coronavírus em humanos: revisão sistemática rápida.

This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.

Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review. / Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática.

OBJECTIVES: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. METHODS: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. RESULTS: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. CONCLUSION: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

Terapia medicamentosa para infecções por coronavírus em humanos: revisão sistemática rápida / Pharmacological therapies for patients with human coronavirus infections: a rapid systematic review

Resumo O objetivo deste trabalho foi avaliar efeitos de tratamentos medicamentosos para infecções por coronavírus. Revisão sistemática rápida com buscas nas bases MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov e International Clinical Trials Registry Platform. Foram incluídos 36 estudos avaliando alternativas medicamentosas contra SARS, SARS-CoV-2 e MERS. A maioria dos estudos incluídos foi conduzida na China com delineamento observacional para tratamento da COVID-19. Os tratamentos mais estudados foram antimaláricos e antivirais. Nos antimaláricos, a metanálise de dois estudos com 180 participantes não identificou benefício da hidroxicloroquina em relação à negativação da carga viral via reação em cadeia de polimerase em tempo real e o uso de antivirais comparado ao cuidado padrão foi similar em relação aos desfechos. As evidências científicas disponíveis são preliminares e de baixa qualidade metodológica, o que sugere cautela na interpretação dos dados. Pesquisas que avaliem a eficácia comparativa em ensaios clínicos randomizados, controlados, com tempo de acompanhamento adequado e com os métodos devidamente divulgados e sujeitos à revisão científica por pares são necessárias. Recomenda-se atualização periódica da presente revisão.

Abstract This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.

Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática / Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review

Resumo O objetivo deste artigo é avaliar a eficácia das máscaras faciais padrão tecido não tecido (TNT) para a prevenção de doenças respiratórias (MERS CoV, SARS-CoV e SARS-CoV-2) na população. Foi realizada busca nas bases de dados Medline, Embase, Cinahl, The Cochrane Library, Trip. Também busca complementar no Google Acadêmico, Rayyan e medRxiv. Não foram aplicados filtros relacionados a data, idioma ou status de publicação. Títulos e resumos foram rastreados e, posteriormente, textos completos foram avaliados. Foram incluídos três estudos: um ensaio clínico randomizado tipo cluster e duas revisões sistemáticas. O ensaio clínico indica benefício potencial de máscaras médicas para controle da fonte de infecção, para a doença respiratória clínica. Em uma das revisões sistemáticas, não foi possível estabelecer relação conclusiva entre uso da máscara e proteção contra infecção respiratória. Por fim, outra revisão sistemática demonstrou que máscaras são eficazes na prevenção da propagação de vírus respiratórios. As evidências apontam para benefício potencial das máscaras faciais padrão TNT. Para o cenário atual de pandemia por COVID 19, recomenda-se educação sobre uso adequado de máscaras, associado a medidas individuais de proteção.

Abstract Objectives: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. Methods: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. Results: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. Conclusion: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

Maternal Exposure to Alcohol and Low Birthweight: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the relationship between maternal exposure to alcohol and low birthweight (LBW). METHODS: The literature search was performed in January 2017 using the following electronic databases: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, and PsychInfo. The search strategy used the following terms: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/use/abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, and cohort studies. No restrictions regarding language or publication date were considered. The literature search yielded 2,383 articles, and after screening and eligibility assessment, 39 articles were included in the systematic review, and 38 studies were included in the meta-analysis. RESULTS: Maternal alcohol consumption was associated with LBW among retrospective cohort studies (relative risk [RR] = 1.37; 95%CI [confidence interval]:1.10-1.77; I2 = 98.4%; p < 0.01). Prospective cohort studies (RR = 1.11; 95%CI: 0.98-1.25; I2 = 81.5%; p < 0.01), and case-control studies (odds ration [OR] = 1.16; 95%CI: 0.68-1.97; I2 = 61.2%; p = 0.05) showed no association between alcohol and LBW. No publication bias was identified, and the meta-regression showed that the sample size influenced the high heterogeneity among retrospective cohort studies. The subgroup analysis showed differences in association between groups when compared by sample size, type of adjustment, or crude measures and publication year. CONCLUSIONS: We have not found an association between alcohol consumption during gestation and LBW in the analysis in all of the subgroups. In addition, we have found a high heterogeneity between the primary studies, which is related to methodological differences in the conduction of these studies.

OBJETIVO: Investigar a associação entre a exposição maternal ao álcool e o baixo peso ao nascer. MéTODO: A busca na literatura ocorreu em janeiro de 2017 nas seguintes bases de dados eletrônicas: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, e PsychInfo. A estratégia de busca utilizou os seguintes termos: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/use/abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, e cohort studies. Não houve restrição de idioma e ano de publicação. A busca na literatura identificou 2.383 artigos, e depois de analisados conforme os critério de elegibilidade, foram incluídos na revisão sistemática 39 estudos, e 38 estudos foram incluídos na metanálise. RESULTADOS: A amostra foi composta por 497.023 gestantes. O consumo materno de álcool foi associado ao baixo peso ao nascer entre os estudos de coorte retrospectiva (risco relativo [RR] = 1,37; IC [intervalo de confiança] 95%: 1,10­1,77; I2 = 98,4%; p < 0,01). Os estudos de coorte prospectiva (RR = 1,11; IC95%: 0,98­1,25; I2 = 81,5%; p < 0,01) e caso-controle (razão de chances [OR, na sigla em inglês] = 1,16; IC95%: 0,68­1,97; I2 = 61,2%; p = 0,05) não apresentaram associação entre o consumo e o desfecho. Não foi identificado viés de publicação, e a metarregressão mostrou que o tamanho da amostra influenciou a heterogeneidade entre os estudos de coorte prospectiva. Na análise por subgrupo, houve diferenças entre os grupos por tamanho de amostra, por tipo de ajuste e por ano de publicação. CONCLUSãO: Não encontramos associação entre o consumo e o baixo peso ao nascer em todas as análises por subgrupo. Além disso, encontramos alta heterogeneidade entre os estudos primários, e isto se deve possivelmente às diferenças metodológicas na condução destes estudos.

Maternal exposure to alcohol and low birthweight: A systematic review and meta-analysis / Exposição maternal ao álcool e baixo peso ao nascer: revisão sistemática e metanálise

Abstract Objective To investigate the relationship between maternal exposure to alcohol and low birthweight (LBW). Methods The literature search was performed in January 2017 using the following electronic databases: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, and PsychInfo. The search strategy used the following terms: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/ use/abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, and cohort studies. No restrictions regarding language or publication date were considered. The literature search yielded 2,383 articles, and after screening and eligibility assessment, 39 articles were included in the systematic review, and 38 studies were included in the meta-analysis. Results Maternal alcohol consumption was associated with LBWamong retrospective cohort studies (relative risk [RR] = 1.37; 95%CI [confidence interval]:1.10-1.77; I2 = 98.4%; p < 0.01). Prospective cohort studies (RR = 1.11; 95%CI: 0.98-1.25; I2 = 81.5%; p < 0.01), and case-control studies (odds ration [OR] = 1.16; 95%CI: 0.68-1.97; I2 = 61.2%; p = 0.05) showed no association between alcohol and LBW.No publication bias was identified, and the meta-regression showed that the sample size influenced the high heterogeneity among retrospective cohort studies. The subgroup analysis showed differences in association between groups when compared by sample size, type of adjustment, or crude measures and publication year. Conclusions We have not found an association between alcohol consumption during gestation and LBW in the analysis in all of the subgroups. In addition, we have found a high heterogeneity between the primary studies, which is related to methodological differences in the conduction of these studies.

Resumo Objetivo Investigar a associação entre a exposição maternal ao álcool e o baixo peso ao nascer. Método A busca na literatura ocorreu em janeiro de 2017 nas seguintes bases de dados eletrônicas: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, e PsychInfo. A estratégia de busca utilizou os seguintes termos: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/use/ abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, e cohort studies. Não houve restrição de idioma e ano de publicação. A busca na literatura identificou 2.383 artigos, e depois de analisados conforme os critério de elegibilidade, foram incluídos na revisão sistemática 39 estudos, e 38 estudos foram incluídos na metanálise. Resultados A amostra foi composta por 497.023 gestantes. O consumo materno de álcool foi associado ao baixo peso ao nascer entre os estudos de coorte retrospectiva (risco relativo [RR] = 1,37; IC [intervalo de confiança] 95%: 1,10-1,77; I2 = 98,4%; p < 0,01). Os estudos de coorte prospectiva (RR = 1,11; IC95%: 0,98-1,25; I2 = 81,5%; p < 0,01) e caso-controle (razão de chances [OR, na sigla em inglês] = 1,16; IC95%: 0,68-1,97; I2 = 61,2%; p = 0,05) não apresentaram associação entre o consumo e o desfecho. Não foi identificado viés de publicação, e a metarregressão mostrou que o tamanho da amostra influenciou a heterogeneidade entre os estudos de coorte prospectiva. Na análise por subgrupo, houve diferenças entre os grupos por tamanho de amostra, por tipo de ajuste e por ano de publicação. Conclusão Não encontramos associação entre o consumo e o baixo peso ao nascer em todas as análises por subgrupo. Além disso, encontramos alta heterogeneidade entre os estudos primários, e isto se deve possivelmente às diferenças metodológicas na condução destes estudos.

Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review.

INTRODUCTION: Mucopolysaccharidosis VI is a rare disease characterized by the arylsulfatase B enzyme deficiency, which is responsible for different clinical manifestations. The treatment consists of enzyme replacement therapy with intravenous administration of galsulfase. OBJECTIVE: Evaluate the effectiveness of the enzyme replacement therapy with galsulfase for the mucopolysaccharidosis VI treatment. METHOD: Systematic review of observational studies. The databases of PubMed, Cochrane Library, Lilacs, and Journal of Inherited Metabolic Disease were reviewed. The selection of studies, data mining, and methodological quality assessment were independently conducted by two authors. RESULTS: Eighteen studies fulfilled the inclusion criteria. Two studies were cohorts, one was longitudinal study, one was cross-sectional, one was a case-control, eight were case series, and five were case reports. A total of 362 participants with mucopolysaccharidosis type VI were evaluated, and 14 different outcomes related to the treatment effect were identified. Seven outcomes showed positive results, characterized by the patient survival, quality of life, respiratory function, joint mobility, physical resistance, reduction of urinary glycosaminoglycans, and growth. The hearing function and the cognitive development were stable after the treatment. Other outcomes related to the cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive outcomes. Concerning safety, light adverse reactions of hypersensitivity were reported. CONCLUSION: This review provided a broader panoramic view of the outcomes related to mucopolysaccharidosis type VI. Regardless of the inherent limitations of observational studies, the outcomes indicate that the enzyme replacement therapy has a positive effect on most of the outcomes associated to the disease.

CD28 is required for T cell activation and IFN-gamma production by CD4+ and CD8+ T cells in response to Trypanosoma cruzi infection.

In the present study we evaluated the mechanisms behind the implication of the costimulatory molecule CD28 for the immune response against the intracellular protozoan parasite Trypanosma cruzi. Our results reveal a critical role for CD28 in the activation of both CD4+ and CD8+ T cells and induction of the effector mechanisms that ultimately mediate the control of parasite growth and pathogenesis in infected mice. CD28-deficient (CD28-/-) mice are highly susceptible to T. cruzi infection, presenting higher parasitemia and tissue parasitism, but less inflammatory cell infiltrate in the heart than C57Bl/6 wild-type (WT) mice. All the infected WT mice survived acute infection, whereas 100% of CD28-/- mice succumbed to it. The increased susceptibility of the CD28-/- mice was associated with a dramatic decrease in the production of IFN-gamma by both CD4+ and CD8+ T cells resulting in a diminished capacity to produce nitric oxide (NO) and mediate parasite killing. T cell activation was also profoundly impaired in CD28-/- mice, which presented decreased lymphoproliferative response after the infection compared to WT mice. Together, these data represent the first evidence that CD28 is critical for efficient CD4+ T cell activation in response to T. cruzi infection in mice.

CTLA-4 blockage increases resistance to infection with the intracellular protozoan Trypanosoma cruzi.

Recent studies have revealed an important role for CTLA-4 as a negative regulator of T cell activation. In the present study, we evaluated the importance of CTLA-4 to the immune response against the intracellular protozoan, Trypanosoma cruzi, the causative agent of Chagas' disease. We observed that the expression of CTLA-4 in spleen cells from naive mice cultured in the presence of live trypomastigote forms of T. cruzi increases over time of exposure. Furthermore, spleen cells harvested from recently infected mice showed a significant increase in the expression of CTLA-4 when compared with spleen cells from noninfected mice. Blockage of CTLA-4 in vitro and/or in vivo did not restore the lymphoproliferative response decreased during the acute phase of infection, but it resulted in a significant increase of NO production in vivo and in vitro. Moreover, the production of IFN-gamma in response to parasite Ags was significantly increased in spleen cells from anti-CTLA-4-treated infected mice when compared with the production found in cells from IgG-treated infected mice. CTLA-4 blockade in vivo also resulted in increased resistance to infection with the Y and Colombian strains of T. cruzi. Taken together these results indicate that CTLA-4 engagement is implicated in the modulation of the immune response against T. cruzi by acting in the mechanisms that control IFN-gamma and NO production during the acute phase of the infection.