ANA CATHARINA DE SEIXAS SANTOS NASTRI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin's lymphoma(2022) PORTO, Victor Bertolo Gomes; CARVALHO, Laina Bubach; BUZO, Bruno Fernando; LITVOC, Marcelo Nobrega; SANTOS, Ana Catharina S.; ROCCI, Rafael Avila; SOARES, Sandra Regina Castro; ZAMPIERI, Ricardo Andrade; DUARTE, Maria Irma Seixas; LINDOSO, Jose Angelo LaulettaVisceral leishmaniasis (VL) is mainly caused by Leishmania (Leishmania) donovani and Leishmania (L.) infantum; however, other Leishmania species have been associated with VL. We report a case of a patient simultaneously diagnosed with VL caused by Leishmania (L.) amazonensis and Hodgkin's lymphoma. After treatment with liposomal amphotericin B and chemotherapy, the patient presented a clinical cure. This case report reinforces the hypothesis that other Leishmania species can cause visceral lesions mainly related to immunosuppression.
- Understanding Sabia virus infections (Brazilian mammarenavirus)(2022) NASTRI, Ana Catharina; DUARTE-NETO, Amaro Nunes; CASADIO, Luciana Vilas Boas; SOUZA, William Marciel de; CLARO, Ingra M.; MANULI, Erika R.; SELEGATTO, Gloria; SALOMA, Matias C.; FIALKOVITZ, Gabriel; TABORDA, Mariane; ALMEIDA, Bianca Leal de; MAGRI, Marcello C.; GUEDES, Ana Rubia; NETO, Laura Vieira Perdigao; SATAKI, Fatima Mitie; GUIMARAES, Thais; MENDES-CORREA, Maria Cassia; TOZETTO-MENDOZA, Tania R.; FUMAGALLI, Marcilio Jorge; HO, Yeh-Li; SILVA, Camila ALves Maia da; COLETTI, Thais M.; JESUS, Jacqueline Goes de; ROMANO, Camila M.; HILL, Sarah C.; PYBUS, Oliver; PINHO, Joao Renato Rebello; LEDESMA, Felipe Lourenco; CASAL, Yuri R.; KANAMURA, Cristina; ARAUJO, Leonardo Jose Tadeu de; FERREIRA, Camila Santos da Silva; GUERRA, Juliana Mariotti; FIGUEIREDO, Luiz Tadeu Moraes; DOLHNIKOFF, Marisa; FARIA, Nuno R.; SABINO, Ester C.; AVANCINI, Venacio; ALVES, Ferreira; LEVIN, Anna S.Background: Only two naturally occurring human Sabi ' a virus (SABV) infections have been reported, and those occurred over 20 years ago. Methods: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. Results: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte ""pinewood knot"" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. Conclusions: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.
- Tegumentary leishmaniasis mimicking visceralization in a cirrhotic patient: atypical cutaneous lesions and local immunological features(2020) VERNAL, Sebastian; CASAL, Yuri; VIEIRA, Lucas T.; AMATO, Valdir S.; DUARTE, Maria Irma S.; NASTRI, Ana Catharina S. S.Tegumentary leislunaniasis (TL) diagnosis is challenging due to the lack of a gold standard diagnostic tool. The diagnosis is significantly harder in regions where visceral leishmaniasis (VL) is also prevalent since immunological tests may present cross-reactivity. A cirrhotic patient from an endemic Brazilian region for TL and VL presented with atypical cutaneous lesions, a usual clinico-laboratory feature of VL (including a positive rk39 test result), but he was diagnosed with TL histopathologically; VL was ruled out by necropsy. Physicians working in co-prevalent areas should be aware of atypical features, unusual clinical course, and unexpected laboratory findings of leishmaniasis.
- Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry(2015) PASSOS-CASTILHO, Ana Maria; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KIKUCHI, Luciana; CHAGAS, Aline Lopes; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda; NASTRI, Ana Catharina de Seixas-Santos; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; GRANATO, Celso Francisco HernandesBackground: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. Methods: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. Results: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. Conclusions: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.
conferenceObject Hepatitis B Virus Prophylaxis and Treatment among Hematopoietic Stem Cell Transplant Recipients: Impact on Engraftment and Outcomes(2020) BUZO, B.; RAMOS, J. Fernandes; ROSSETTI, R. Marques; SALLES, N.; MENDRONE-JUNIOR, A.; ROCHA, V.; NASTRI, A. de Seixas SantosconferenceObject HIV CO-INFECTION IS AN INDEPENDENT FACTOR IN DETERMINING VACCINE SCAPE MUTANTS AMONG HEPATITIS B CHRONIC PATIENTS IN BRAZIL(2012) MENDES-CORREA, M. C.; PINHO, J. R. R.; GOMES-GOUVEA, M. S.; CHACHA, S.; MARTINELLI, A. L. C.; GUASTINI, C. F.; SANTOS, A. C. S.; SOARES, M. C. P.; LEITE, O. H. M.; UIP, D. E.Background: Prolonged lamivudine (LAM) therapy has been associated with different mutations in the hepatitis B virus (HBV) genome. The aims of this study were: (1) to compare lamivudine-resistance mutation patterns after prolonged LAM use between patients with chronic hepatitis B infection (CHB) with or without human immunodeficiency virus (HIV) co-infection; (2) to evaluate the incidence and factors associated with the presence of mutations in the envelope gene among these patients. Methods: We included patients with CHB treated with LAM and with detectable HBV-DNA (>50IU/mL) after at least six months of LAM use. HBV load was determined using an “in-house” real-time polymerase chain reaction. HBV mutation status analysis were carried out by amplification and sequencing the complete HBV RT-domain. Results: Ninety-one patients infected only with HBV and 34 HIV-HBV co-infected patients were included. The time of exposure to LAM varied from 7 to 140 months among HBV infected patients and from 12 to 182 months among co-infected patients. Mutations associated with resistance to LAM were observed in 42.9% of HBV infected patients and in 67.6% of HIV-HBV co-infected patients. In this latter group, the frequency of the rtV173L + rtL180M + rtM204V triple mutation was 32.0% versus 7.6% observed among patients infected only with HBV. All patients with this triple mutational pattern also showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that time of exposure to lamivudine superior of 32 months (adjusted PR 1.51, 95%CI 1.10–2.06) was an independent variable associated with the chance of harboring mutations in the polymerase gene. Multivariate analysis also demonstrated that HIV co-infection (adjusted PR 1.40, 95%CI 1.10–1.78) was the only independent variable associated with the chance of harboring sE164D or I195M changes in the envelope gene (vaccine escape phenotype). Conclusions: Prolonged use of LAM may be associated with multiple changes in the pol gene, among mono or co-infected patients; 2-HIV co-infection is an independent factor in determining sE164D and I195M changes in the envelope gene, a vaccine escape phenotype.- The Molecular Characterization of Hepatitis A Virus Strains Circulating during Hepatitis A Outbreaks in Sao Paulo, Brazil, from September 2017 to May 2019(2022) CHUFFI, Samira; GOMES-GOUVEA, Michele S.; CASADIO, Luciana V. B.; NASTRI, Ana Catharina S. S.; GONZALEZ, Mario P.; COTIA, Andre L. F.; ARANDA, Amanda G. D.; TENORE, Simone B.; ONO, Suzane K.; MALTA, Fernanda M.; MADALOSSO, Geraldine; FERREIRA, Paulo R. A.; CARRILHO, Flair J.; PINHO, Joao R. R.Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an outbreak involved approximately 22 European countries with 4475 cases reported from 2016 to 2018; most of them were men who have sex with men (MSM). This outbreak expanded to North and South America, including Brazil, particularly in Sao Paulo city with 1547 reported cases from 2016 to 2019. In the present study, we characterized the HAV strains involved in the acute hepatitis A cases identified in the reference centers of Sao Paulo city during this outbreak. A total of 51 cases with positive anti-HAV IgM were included, 80.4% male, 68.6% of them between 20 and 40 years old and 41.7% MSM. HAV RNA was detected in 92% (47/51) of the cases. Subgenotype IA of HAV was identified and most of the strains were closely related to that isolated in outbreaks that occurred in different European countries in 2016. These results showed the epidemiological relation between these outbreaks and reinforce the need to implement vaccination against hepatitis A for the adult population, particularly for a population with a high-risk behavior.
- Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure(2019) MENDES, Erica Araujo; PILGER, Denise Regina Bairros de; NASTRI, Ana Catharina de Seixas Santos; MALTA, Fernanda de Mello; PASCOALINO, Bruno dos Santos; D'ALBUQUERQUE, Luiz Augusto Carneiro; BALAN, Andrea; JR, Lucio Holanda Gondim de Freitas; DURIGON, Edison Luis; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloIntroduction and objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). Materials and methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment. (C) 2019 Fundacion Clinica Medica Sur, A.C.
- Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up(2017) MACHADO, Soraia Mafra; ALMEIDA-NETO, Cesar de; PINHO, Joao Renato Rebello; MALTA, Fernanda de Mello; CAPUANI, Ligia; CAMPOS, Aleia Faustina; ABREU, Fatima Regina Marques; NASTRI, Ana Catharina de Seixas Santos; SANTANA, Rbia Anita Ferraz; SABINO, Ester Cerdeira; MENDES-CORREA, Maria CassiaOBJECTIVE: To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS: Blood donors from 1994 to 2012, identified with positive anti-HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS: Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95% CI 1.15-1.71), age under or equal to 50 years (PR = 1.36; 95% CI 1.12-1.65) and non-Caucasians (PR = 1.53; 95% CI 1.27-1.84). CONCLUSIONS: About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments.
- Sabia Virus-Like Mammarenavirus in Patient with Fatal Hemorrhagic Fever, Brazil, 2020(2020) MALTA, Fernanda de Mello; AMGARTEN, Deyvid; NASTRI, Ana Catharina de Seixas Santos; HO, Yeh-Li; CASADIO, Luciana Vilas Boas; BASQUEIRA, Marcela; SELEGATTO, Gloria; CERVATO, Murilo Castro; DUARTE-NETO, Amaro Nunes; HIGASHINO, Hermes Ryoiti; MEDEIROS, Felipe Arthur Faustino; GENDLER, Jose Luiz Pinto Lima; LEVIN, Anna S.; PINHO, Joao Renato RebelloNew World arenaviruses can cause chronic infection in rodents and hemorrhagic fever in humans. We identified a Sable virus-like mammarenevirus in a patient with fatal hemorrhagic fever from Sao Paulo, Brazil. The virus was detected through virorne enrichment and metagenomic next-generation sequencing technology.