MARIA APARECIDA SHIKANAI YASUDA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
LIM/48 - Laboratório de Imunologia, Hospital das Clínicas, Faculdade de Medicina
LIM/48 - Laboratório de Imunologia, Hospital das Clínicas, Faculdade de Medicina
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- Bloodstream infection in hematopoietic stem cell transplantation outpatients: risk factors for hospitalization and death(2019) RUSSO, Rachel; MENDES, Elisa Teixeira; LEVIN, Anna Sara; DULLEY, Frederico; OLIVEIRA, Maura S.; SHIKANAI-YASUDA, Maria Aparecida; COSTA, Silvia FigueiredoWe described 235 bloodstream infection (BSI) episodes in 146 hematopoietic stem cell transplantation (HSCT) outpatients and evaluated risk factors for hospitalization and death. Records of outpatients presenting with positive blood cultures over a 5-year period (January 2005 to December 2008) were reviewed. Variables with p< 0.1 in bivariate analysis were used in a regression logistic model. A total of 266 agents were identified, being 175 (66.7%) gram-negative. 80 (30.3%) gram-positive bacteria and 9 (3.4%) fungi. The most common underlying disease was acute leukemia 40 (27.4%), followed by lymphoma non-Hodgkin 26 (18%) and 87 patients (59.6%) were submitted to allogeneic hematopoietic stem cell transplant (HSCT). BSI episodes were more frequent during the first 100 days after transplantation (183 or 77.8%), and ninety-one (38.7%) episodes of BSI occurred up to the first 30 days. Hospitalization occurred in 26% of the episodes and death in 10% of cases. Only autologous HSCT was protector for hospitalization. Although. central venous catheter (CVC) withdrawal and the Multinational Association of Supportive Care in Cancer (MASCC) score up to 21 points were protector factors for death in the bivariate analysis, only MASCC remained as protector.
- A Real Time PCR strategy for the detection and quantification of Candida albicans in human blood(2020) BUSSER, Felipe Delatorre; COELHO, Vivian Caso; FONSECA, Claudia de Abreu; NEGRO, Gilda Maria Barbaro Del; SHIKANAI-YASUDA, Maria Aparecida; LOPES, Marta Heloisa; MAGRI, Marcello Mihailenko Chaves; FREITAS, Vera Lucia Teixeira deCandidemia is a significant cause of bloodstream infections (BSI) in nosocomial settings. The identification of species can potentially improve the quality of care and decrease human mortality. Quantitative PCR (qPCR) was evaluated for Candida albicans detection using culture suspensions containing C. albicans, spiked human blood. the cloned qPCR target fragment (ITS2 region) and the results of these assays were compared. The assays showed a good detection limit: C. albicans DNA extracted from yeast (sensitivity 0.2 CFU/mu L), spiked human blood (sensitivity 10 CFU/mL), and cloned fragment of ITS2 region (sensitivity 20 target copies/mu L). The efficiency of ITS2 fragment-qPCR ranged from 89.67 to 97.07, and the linearity (R-2) of the standard curve ranged from 0.992 to 0.999. The results showed that this ITS2-qPCR has a great potential as a molecular prototype model for the development of a test to be applied in clinical practice, greatly reducing the time of candidemia diagnosis, which is extremely important in this clinical setting.
- Seroconversion of 2009 pandemic influenza A (H1N1) vaccination in kidney transplant patients and the influence of different risk factors(2013) AZEVEDO, L. S.; GERHARD, J.; MIRAGLIA, J. L.; PRECIOSO, A. R.; TIMENETSKY, M. dC S. Tavares; AGENA, F.; GAMBA, C.; YASUDA, M. A. Shikanai; DAVID-NETO, E.; PIERROTTI, L.BackgroundInfluenza may present a high morbidity and mortality in solid organ transplanted patients (SOTP). Annual influenza virus vaccine is recommended for SOTP. However, low levels of seroconversion in SOTP have been reported. The aim of this study was to evaluate the immunogenicity of 2009 pandemic influenza A (H1N1) - A(H1N1)pdm09 - vaccine in kidney transplant patients and to analyze which features might affect seroconversion. MethodsThis study was conducted from March to August 2010 at the Renal Transplantation Unit of University of SAo Paulo, Brazil. A total of 85 renal transplant patients attending the outpatient unit received one 15-g intramuscular dose of A(H1N1)pdm09 influenza vaccine (reassortant vaccine virus A/California/7/2009 [NYMC X-179A]). Blood samples were collected immediately before and 21days after the vaccine was given. Antibody response was measured by the standard hemagglutination-inhibition (HI) assay. The primary immunogenicity endpoint for this study was seroconversion in previously seronegative patients (HI titers <1:40), and the secondary endpoint was the identification of features that could affect seroconversion in this population. ResultsFive (5.9%) patients presented HI titers prevaccination 1:40 and were excluded from further analysis. Seroconversion in previously negative patients occurred in 27 (34%) of 80 patients. Prevaccination HI titers geometrical mean was 5.8 and postvaccination 19.6 (ratio 3.4). Significant seroconversion rate factors were female gender, non-Caucasian ethnicity, and post-transplant time before vaccination. No impact was seen on seroconversion for age, donor type, tacrolimus and cyclosporine blood levels, renal function, or blood lymphocyte counts. Mycophenolate (MPA) showed a lower rate of seroconversion when compared with azathioprine. Tacrolimus and cyclosporine had similar seroconversion rates. Sirolimus use was associated with the highest rate of seroconversion, although these patient numbers were low. Immunosuppresssion containing MPA was considerably less effective in seroconversion than drug combinations with no MPA. Patients receiving sirolimus had more chance of seroconversion. HI titers geometric means pre/post vaccine were as follows: MPA (n=56): 5.8/12.8; tacrolimus (n=50): 5.9/16.2; cyclosporine (n=18): 5.4/24.2; azathioprine (n=19): 6.2/51.6; and sirolimus (n=6): 8/80. By univariate analysis, being female and non-White were variables associated with 3.3 times more chance of seroconversion than being male and White. In the multivariate analysis, the variables remaining in the model showed similar hazard ratios. ConclusionsIn this study, the monovalent A(H1N1)pdm09 influenza vaccine demonstrated low rates of seroconversion, particularly in patients on MPA, but with potentially higher response rates in patients on sirolimus.
- II Consenso Brasileiro em Doença de Chagas, 2015(2016) DIAS, João Carlos Pinto; RAMOS JR., Alberto Novaes; GONTIJO, Eliane Dias; LUQUETTI, Alejandro; SHIKANAI-YASUDA, Maria Aparecida; COURA, José Rodrigues; TORRES, Rosália Morais; MELO, José Renan da Cunha; ALMEIDA, Eros Antonio de; OLIVEIRA JR., Wilson de; SILVEIRA, Antônio Carlos; REZENDE, Joffre Marcondes de; PINTO, Fabiane Scalabrini; FERREIRA, Antonio Walter; RASSI, Anis; FRAGATA FILHO, Abílio Augusto; SOUSA, Andréa Silvestre de; CORREIA FILHO, Dalmo; JANSEN, Ana Maria; ANDRADE, Glaucia Manzan Queiroz; BRITTO, Constança Felícia De Paoli de Carvalho; PINTO, Ana Yecê das Neves; RASSI JR., Anis; CAMPOS, Dayse Elisabeth; ABAD-FRANCH, Fernando; SANTOS, Silvana Eloi; CHIARI, Egler; HASSLOCHER-MORENO, Alejandro Marcel; MOREIRA, Eliane Furtado; MARQUES, Divina Seila de Oliveira; SILVA, Eliane Lages; MARIN-NETO, José Antonio; GALVÃO, Lúcia Maria da Cunha; XAVIER, Sergio Salles; VALENTE, Sebastião Aldo da Silva; CARVALHO, Noêmia Barbosa; CARDOSO, Alessandra Viana; SILVA, Rafaella Albuquerque e; COSTA, Veruska Maia da; VIVALDINI, Simone Monzani; OLIVEIRA, Suelene Mamede; VALENTE, Vera da Costa; LIMA, Mayara Maia; ALVES, Renato VieiraABSTRACT Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.
- CURRENT TREATMENT OPTIONS FOR INVASIVE ASPERGILLOSIS(2013) BATISTA, M. V.; COSTA, S. F.; SHIKANAI-YASUDA, M. A.; MOSS, R. B.Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in immunocom promised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplant recipients. The optimal therapy for invasive aspergillosis relies on the restoration of leukocyte counts and effective antifungal treatment initiated at the earliest stage of infection. Several alternative antifungal compounds are currently available. A rational approach should take into account not only the degree of certainty of infection (as codified by the EORTC/MSG classification), but also previous exposure to other antifungals, the pharmacokinetic and pharmacodynamic characteristics of the antifungals employed and the clinical characteristics of the patient.
- Paracoccidioidomycosis: eco-epidemiology, taxonomy and clinical and therapeutic issues(2013) BOCCA, Anamelia Lorenzetti; AMARAL, Andre Correa; TEIXEIRA, Marcus Melo; SATO, Paula; SHIKANAI-YASUDA, Maria Aparecida; FELIPE, Maria Sueli SoaresAcquired by inhalation of the thermal dimorphic fungi Paracoccidioides spp. conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially fatal disseminated disease. The main focus of this review is to highlight clinical aspects of paracoccidioidomycosis and, its pathogens' diversity ecology and particularities. In addition, we present strategies for therapy, including DNA vaccines and nanostructured drugs. Molecular and morphological data supported the split of the Paracoccidioides genus into two species, Paracoccidioides brasiliensis and Paracoccidioides lutzii. An acute form of the disease affects approximately 5% of cases and involves the phagocytic mononuclear system, resulting in progressive lymphadenopathy. The chronic form affects adult men and frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal glands. The clinical manifestations depend on the ability of the host to control the fungal multiplication and dissemination. The long survival time of the fungus in the host tissues allows it to evade immune responses; therefore, successful treatment often requires long-time therapy. The consensus for treatment must consider the severity of the disease and includes sulfone derivatives, amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines and nanostructured drugs are also presented and discussed in this review.
conferenceObject CHAGAS DISEASE CARDIOMYOPATHY: ASSOCIATION WITH IL-17 AND IL-18 GENETIC POLYMORPHISMS(2018) SANTOS, Alexandra dos; FERREIRA, Daiane; OLIVEIRA, Jamile; OLIVEIRA, Claudia; BOCCHI, Edimar; NOVAES, Cristina; CRUZ, Fatima; CARVALHO, Noemia; SATO, Paula; FREITAS, Vera; SHIKANAI-YASUDA, Maria- Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?(2014) MASSARO, K. S. R.; MACEDO, R.; CASTRO, B. S. de; DULLEY, F.; OLIVEIRA, M. S.; YASUDA, M. A. S.; LEVIN, A. S.; COSTA, S. F.The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73 %) autologous and 80 (20 %) allogeneic were assessed. One hundred and ninety (64.2 %) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4 %). Twenty-three cases (7.8 %) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 > 140 pg/mL and CRP a parts per thousand yen120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH a parts per thousand yen390 UI/L, urea a parts per thousand yen25 mg/dL and CRP a parts per thousand yen120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP a parts per thousand yen120 mg/L for allogeneic HSCT, however, CRP a parts per thousand yen120 mg/L did not remain in the model when urea a parts per thousand yen25 mg/L was included. No independent risk factor was found for autologous patients. Out of the biomarkers assessed, only CRP a parts per thousand yen120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH a parts per thousand yen390 UI/L and urea a parts per thousand yen25 mg/dL. For allogeneic patients only CRP a parts per thousand yen120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea a parts per thousand yen25 mg/L was included.
- Immunoproteome of Aspergillus fumigatus Using Sera of Patients with Invasive Aspergillosis(2014) VIRGINIO, Emylli D.; KUBITSCHEK-BARREIRA, Paula H.; BATISTA, Marjorie Vieira; SCHIRMER, Marcelo R.; ABDELHAY, Eliana; SHIKANAI-YASUDA, Maria A.; LOPES-BEZERRA, Leila M.Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of Platelia (TM) Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS). A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units.
- Multilocus Sequence Typing of Candida tropicalis Shows the Presence of Different Clonal Clusters and Fluconazole Susceptibility Profiles in Sequential Isolates from Candidemia Patients in Sao Paulo, Brazil(2013) MAGRI, Marcello Mihailenko Chaves; GOMES-GOUVEA, Michele Soares; FREITAS, Vera Lucia Teixeira de; MOTTA, Adriana Lopes; MORETTI, Maria Luiza; SHIKANAI-YASUDA, Maria AparecidaThe profiles of 61 Candida tropicalis isolates from 43 patients (28 adults and 15 children) diagnosed with candidemia at two teaching hospitals in Sao Paulo, Brazil, were characterized by multilocus sequence typing (MLST). For the 14 patients who had bloodstream infections, 32 isolates were serially collected from their blood and/or catheters. Thirty-nine diploid sequence types (DSTs) were differentiated. According to the C. tropicalis MLST database (http://pubmlst.org/ctropicalis/), 36 DSTs and 23 genotypes identified from the 61 isolates had not previously been described. This report represents the first study to characterize sequential isolates of C. tropicalis from candidemia cases in South America. Microvariation in a single gene was found in the sequential isolates from 7 patients. The main polymorphisms occurred in the alleles of the XYR1 gene, specifically at nucleotide positions 215, 242, and 344. Macrovariation in six gene fragments was detected in the isolates from 3 patients. eBURST analysis added two new groups to this study (groups 6 and 18). Additionally, susceptibility tests indicate that 3 isolates were resistant to fluconazole. No correlation was found between the DSTs and susceptibility to fluconazole and/or selective antifungal pressure. Two patients were sequentially infected with resistant and susceptible strains. MLST is an important tool for studying the genetic diversity of multiple/sequential isolates of patients with candidemia, allowing the comparison of our data with those from other regions of the world, as well as allowing an analysis of the genetic relationship among several clones in sequential isolates from the same or different candidemia patient sites (blood or catheter).