Publications by authors named "George T Diniz"

6 Publications

  • Page 1 of 1

Assessment of a recombinant protein from Leishmania infantum as a novel tool for Visceral Leishmaniasis (VL) diagnosis in VL/HIV co-infection cases.

PLoS One 2021 17;16(5):e0251861. Epub 2021 May 17.

Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil.

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128258PMC
May 2021

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

Human leukocyte antigen-G 3' untranslated region polymorphism +3142G/C (rs1063320) and haplotypes are associated with manifestations of the American Tegumentary Leishmaniasis in a Northeastern Brazilian population.

Hum Immunol 2019 Nov 13;80(11):908-916. Epub 2019 Aug 13.

Immunogenetic Laboratory, Immunology Department, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Av. Moraes rego, s/n, Campus da UFPE, Cidade Universitária, Recife, PE CEP:50670-465, Brazil. Electronic address:

While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.
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http://dx.doi.org/10.1016/j.humimm.2019.08.001DOI Listing
November 2019

Performance evaluation of anti-fixed Leishmania infantum promastigotes immunoglobulin G (IgG) detected by flow cytometry as a diagnostic tool for visceral Leishmaniasis.

J Immunol Methods 2019 06 25;469:18-25. Epub 2019 Feb 25.

Fundação Oswaldo Cruz (Fiocruz-Pernambuco), Instituto Aggeu Magalhães, Recife, Pernambuco, Brazil.

Visceral Leishmaniasis (VL) is a severe disease, caused by the protozoans Leishmania infantum and L. donovani that is widely diagnosed using serological tools. These, however, have limitations in performance that limit their use for the correct identification of the cases. This study aimed to evaluate the performance of flow cytometry with fixed parasites for VL diagnosis, comparing it with four other serological tests. Samples from two endemic VL regions in Brazil, diagnosed by direct examination (DG1) and by at least two or one standard serological test (DG2 and DG3, respectively), as well as patients with chronic Chagas' disease (CG1) and healthy controls (CG2) were used in this study. The flow cytometry results were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). Using a 1:4096 serum dilution, a ROC curve analysis of the serum titration on flow cytometry has indicated a PPFP of 2% as the cutoff point to segregate positive and negative results. In the present study, flow cytometry had the best performance for DG1 (sensitivity of 96%) while rK39 (imunocromagraphic rapid test) and DAT (Direct agglutination test) were also associated with high sensitivity and specificity. The substantial agreement and kappa indexes observed suggested similar performances between these two tests and flow cytometry. IFAT (Immunofluorescent antibody test) and ELISA (Enzyme-linked immunosorbent assay) had lower performances and the lower values of agreement with flow cytometry. Together, these findings suggest that although adjustments are needed in order to reduce cross reactivity with other trypanosomatids, flow cytometry has the potential to be a safe serological alternative for the diagnosis of VL.
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http://dx.doi.org/10.1016/j.jim.2019.02.009DOI Listing
June 2019

Is it better to be rich in a poor area or poor in a rich area? A multilevel analysis of a case-control study of social determinants of tuberculosis.

Int J Epidemiol 2009 Oct 4;38(5):1285-96. Epub 2009 Aug 4.

Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.

Background: Tuberculosis is known to have socio-economic determinants at individual and at area levels, but it is not known whether they are independent, whether they interact and their relative contributions to the burden of tuberculosis.

Methods: A case-control study was conducted in Recife, Brazil, to investigate individual and area social determinants of tuberculosis, to explore the relationship between determinants at the two levels and to calculate their relative contribution to the burden of tuberculosis. It included 1452 cases of tuberculosis diagnosed by the tuberculosis services and 5808 controls selected at random from questionnaires completed for the demographic census. Exhaustive information on social factors was collected from cases, using the questionnaire used in the census. Socio-economic information for areas was downloaded from the census. Multilevel logistic regression investigated individual and area effects.

Results: There was a marked and independent influence of social variables on the risk of tuberculosis, both at individual and area levels. At individual level, being aged >or=20, being male, being illiterate, not working in the previous 7 days and possessing few goods, all increased the risk of tuberculosis. At area level, living in an area with many illiterate people and where few households own a computer also increased this risk; individual and area levels did not appear to interact. Twice as many cases were attributable to social variables at individual level than at area level.

Conclusions: Although individual characteristics are the main contributor to the risk of tuberculosis, contextual characteristics make a substantial independent contribution.
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http://dx.doi.org/10.1093/ije/dyp224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755128PMC
October 2009