Publications by authors named "Silvia M L Montenegro"

14 Publications

  • Page 1 of 1

The Coutinho index as a simple tool for screening patients with advanced forms of Schistosomiasis mansoni: a validation study.

Trans R Soc Trop Med Hyg 2021 Mar 16. Epub 2021 Mar 16.

Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil.

Background: Periportal fibrosis (PPF) is the major pathological consequence of Schistosoma mansoni infection. The Coutinho index-the alkaline phosphatase (ALP) to platelet ratio ([ALP/upper limit of normality {ULN}]/platelet count [106/L] x 100)-was validated. Validation consisted of modest laboratory tests to predict advanced PPF.

Methods: A total of 378 individuals from an endemic area of Brazil with a previous history of the disease and/or a positive parasitological examination were evaluated. We used ultrasound examination as the gold standard for classification of the PPF pattern and measured the biological markers of the index.

Results: Forty-one individuals (10.8%) without PPF, 291 (77%) with moderate PPF and 46 (12.2%) with advanced PPF, were identified. ALP and platelet count were used for the index. The cut-off point ≥0.228 predicted the presence of fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.56, sensitivity of 68.6% and specificity of 46.3%. There was an absence of PPF in 46.3% of individuals without fibrosis and the presence of PPF in 68.5% of cases with moderate and advanced ultrasound fibrosis. The identification of advanced fibrosis with a cut-off point ≥0.316 revealed an AUROC curve of 0.70, sensitivity of 67.4% and specificity of 68.3%, thus confirming the advanced phase in 65.2% of cases compared with ultrasound.

Conclusion: The Coutinho index was able to predict advanced PPF in most individuals. It is valid as a new tool, uses routine laboratory tests and therefore is more accessible for screening patients with a severe form of the disease in endemic areas.
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http://dx.doi.org/10.1093/trstmh/trab040DOI Listing
March 2021

Evaluation of the influence of global DNA methylation level in patients with acute coronary syndrome.

Clin Chim Acta 2020 Dec 15;511:336-341. Epub 2020 Oct 15.

Aggeu Magalhães Institute - Fiocruz/PE, Recife, Pernambuco, Brazil.

DNA methylation is one of the mechanisms of epigenetic regulation and is observed in mammals to maintain a normal expression pattern of the genes. Aberrant profiles of DNA methylation have already been associated with cardiovascular diseases. We evaluated 190 patients with Acute Coronary Syndrome (ACS) and 75 patients without ACS (non-ACS). Patient severity was assessed by the TIMI risk score, and both levels of global DNA methylation (ACS = 190; non-ACS = 75), stratified in expected group (male ≥ 65 years; female ≥ 55 years) and early group (male < 65 years; female < 55 years). As results, the ACS and non-ACS groups showed different levels of global DNA methylation, and patients with ACS were more methylated (p = 0.0121). Patients with ACS, showed a difference (p < 0.0001) in methylation profiles between groups. The low TIMI group had a higher level of DNA methylation, while the intermediate / high group showed a decreased methylation pattern. A negative correlation was observed between the level of global methylation and the increase in age (p = 0.0387; r = -0.15), which became hypomethylated over the years. The hypermethylated global DNA profile by its association with the development of ACS can be a potential biomarker.
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http://dx.doi.org/10.1016/j.cca.2020.10.016DOI Listing
December 2020

T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

PLoS Negl Trop Dis 2013 31;7(1):e1938. Epub 2013 Jan 31.

Virology and Experimental Therapeutics Laboratory, Aggeu Magalhães Research Center, Fiocruz, Recife, Pernambuco, Brazil.

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+) and CD8(+) T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.
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http://dx.doi.org/10.1371/journal.pntd.0001938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561163PMC
June 2013

Genetic susceptibility to chronic Chagas disease: an overview of single nucleotide polymorphisms of cytokine genes.

Cytokine 2012 Aug 15;59(2):203-8. Epub 2012 May 15.

Department of Immunology, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil.

Chagas disease is a parasitic infection that is a significant public health problem in Latin America. The mechanisms responsible for susceptibility to the infection and the mechanisms involved in the development of cardiac and digestive forms of chronic Chagas disease remain poorly understood. However, there is growing evidence that differences in susceptibility in endemic areas may be attributable to host genetic factors. The aim of this overview was to analyze the genetic susceptibility to human Chagas disease, particularly that of single nucleotide polymorphisms of cytokine genes. A review of the literature was conducted on the following databases: PubMed/MEDLINE and Scopus. The search strategy included using the following terms: "Cytokines", "Single Nucleotide Polymorphisms" and "Chagas Disease". After screening 25 citations from the databases, 19 studies were selected for the overview. A critical analysis of the data presented in the articles suggests that genetic susceptibility to Chagas disease and chronic Chagas cardiomyopathy is highly influenced by the complexity of the immune response of the host. Follow-up studies based on other populations where Chagas disease is endemic (with distinct ethnic and genetic backgrounds) need to be conducted. These should use a large sample population so as to establish what cytokine genes are involved in susceptibility to and/or progression of the disease.
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http://dx.doi.org/10.1016/j.cyto.2012.04.035DOI Listing
August 2012

Identification of continuous human B-cell epitopes in the envelope glycoprotein of dengue virus type 3 (DENV-3).

PLoS One 2009 Oct 13;4(10):e7425. Epub 2009 Oct 13.

Virology and Experimental Therapy Laboratory, Aggeu Magalhães Research Center, Fiocruz, Recife, Pernambuco, Brazil.

Background: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes.

Methodology/principal Findings: Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively.

Conclusions/significance: Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007425PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760205PMC
October 2009

Discriminating acute from chronic human schistosomiasis mansoni.

Acta Trop 2008 Nov-Dec;108(2-3):229-33. Epub 2008 Sep 18.

Instituto Oswaldo Cruz-Fiocruz, Av. Brasil 4365-900, Rio de Janeiro, RJ, Brazil.

Specific immunoglobulin (IgA, IgG and IgM) responses to different antigen targets (soluble eggs antigen--SEA, soluble worm adult protein--SWAP and keyhole limpet hole--KLH) were measured by enzyme linked immunosorbent assay (ELISA) in patients with acute and chronic schistosomiasis, as well as patients without schistosomiasis. SEA IgA and KLH IgM presented high discriminatory powers to distinguish acute from chronic schistosomiasis, with calculated areas under the curve (AUCs) of 0.88 and 0.82, respectively, obtained from receiver operating characteristic (ROC) curve. On the other hand, these tests, particularly SEA IgA were not useful to distinguish schistosomiasis (including the acute and chronic forms) from individuals without this disease, but infected with other intestinal parasites (Ascaris lumbricoides, Trichuris trichiura and hookworm). By contrast, SWAP IgG and SEA IgG were able to discriminate schistosomiasis patients from healthy individuals and patients infected with other parasites (AUCs of 0.96 and 0.85, respectively). Thus, it is possible to use a combination of serological tests, such as SEA IgA and SWAP IgG, to simultaneously establish the diagnosis of schistosomiasis and discriminate the acute from the chronic forms of the disease.
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http://dx.doi.org/10.1016/j.actatropica.2008.08.012DOI Listing
January 2009

Preliminary results in the immunodiagnosis of tuberculosis in children based on T cell responses to ESAT-6 and PPD antigens.

Mem Inst Oswaldo Cruz 2008 Jun;103(4):401-4

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães-Fiocruz, Recife, PE, Brasil.

The aim of this work was to study the difference in interferon gamma (IFN-gamma) production by T lymphocytes after early secretory antigen target 6 (ESAT-6) or purified protein derivate (PPD) stimulation in whole blood culture supernatants from children with suspected tuberculosis (TB) disease (n = 21), latent TB infection (n = 16) and negative controls (NC) (n = 22) from an endemic area in Brazil. The concentration of IFN-gamma (pg/ml) was measured by enzyme linked immunosorbent assay and the differences in the IFN-gamma levels for each group were compared and evaluated using an unpaired Student's t-test; p values < 0.05 were considered significant. Measurement of IFN-gamma levels after ESAT-6 stimulation raised the possibility of early diagnosis in the latent TB group (p = 0.0030). Nevertheless, the same group showed similar responses to the NC group (p > 0.05) after PPD stimulation. The IFN-gamma assay using ESAT-6 as an antigenic stimulus has the potential to be used as a tool for the immunodiagnosis of early TB in children.
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http://dx.doi.org/10.1590/s0074-02762008000400015DOI Listing
June 2008

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens.

Mem Inst Oswaldo Cruz 2007 May;102(2):225-8

Departamento de Bioquímica, Universitária, 52020-020 Recife, PE, Brasil.

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.
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http://dx.doi.org/10.1590/s0074-02762007005000002DOI Listing
May 2007

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection.

Mem Inst Oswaldo Cruz 2006 Sep;101 Suppl 1:353-4

Centro de Pesquisas Aggeu Magalhães-Fiocruz, Av. Prof. Moraes Rego, 52020-020 Recife, PE, Brazil.

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.
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http://dx.doi.org/10.1590/s0074-02762006000900057DOI Listing
September 2006

Immunopathogenic mechanisms in schistosomiasis: what can be learnt from human studies?

Trends Parasitol 2006 Feb 27;22(2):85-91. Epub 2005 Dec 27.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Avenida Professor Moraes Rego s/n, Cidade Universitária, 50670-420 Recife, Brazil.

Studies in mice indicate that schistosome egg-induced granuloma formation and hepatic fibrosis depend markedly on cytokine regulation, with interleukin 10 having a central role. There is no clear consensus about the pattern of cytokine production and regulation that causes a minority of chronically exposed patients to develop severe hepatosplenic (HS) disease, which is characterized by periportal fibrosis and portal hypertension. HS disease and the progression of hepatic fibrosis are associated with the production of profibrotic type 2 cytokines in the early stages of infection with Schistosoma mansoni. However, other studies indicate that HS disease is characterized by a predominant T helper 1 profile. Until new tools and approaches are developed to study human disease in endemic areas, investigators must either speculate about indirect evidence from human studies or rely more heavily on findings generated from experimental models of the disease.
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http://dx.doi.org/10.1016/j.pt.2005.12.004DOI Listing
February 2006

Evaluation of tests based on the antibody response to keyhole limpet haemocyanin and soluble egg antigen to differentiate acute and chronic human schistosomiasis mansoni.

Mem Inst Oswaldo Cruz 2004 13;99(5 Suppl 1):97-8. Epub 2004 Oct 13.

Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brazil.

Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.
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http://dx.doi.org/10.1590/s0074-02762004000900017DOI Listing
February 2005

Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human Schistosomiasis mansoni.

Mem Inst Oswaldo Cruz 2002 ;97 Suppl 1:113-4

Centro de Pesquisas Aggeu Magalhães, Fiocruz, Recife, PE, 50670-420, Brasil.

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific.
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http://dx.doi.org/10.1590/s0074-02762002000900023DOI Listing
February 2003

Partial molecular characterization of Sm8, a tegumental antigen of Schistosoma mansoni.

Mem Inst Oswaldo Cruz 2002 ;97 Suppl 1:91-3

Centro de Pesquisas Aggeu Magalhães, Fiocruz, Recife, PE, 50670-420, Brasil.

Sm8 is a major tegumental antigen of Schistosoma mansoni. The partial cDNA was isolated and analyzed. Sequence analysis revealed transmembrane compatible hydrophobic domains and a putative leucine zipper pattern. The mRNA and the protein are predominantly expressed in adult worms.
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http://dx.doi.org/10.1590/s0074-02762002000900018DOI Listing
February 2003

Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis.

Infect Immun 2002 Nov;70(11):5903-12

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães-FIOCRUZ. Universidade Federal de Pernambuco, Recife, Brazil.

Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC130279PMC
http://dx.doi.org/10.1128/IAI.70.11.5903-5912.2002DOI Listing
November 2002
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