Doutorado em Medicina Tropical e Saúde Pública (IPTSP)

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Prevalência e fatores associados aos comportamentos de risco para doenças crônicas não transmissíveis em adolescentes e adultos jovens do Brasil
(Universidade Federal de Goiás, 2024-09-03) Pedroso, Charlise Fortunato; Guimarães , Rafael Alves; http://lattes.cnpq.br/7847112412490217; Guimarães, Rafael Alves; Afonso, Eliane Terezinha; Vieira, Maria Aparecida da Silva; Cavalcante , Agueda Maria Ruiz Zimmer; Vieira, Nayara Figueiredo
Title: Prevalence and factors associated with disease risk behaviors non-communicable diseases in adolescents and young adults in Brazil Introduction: Unhealthy lifestyle behaviors such as smoking, alcohol consumption, unhealthy diet, physical inactivity and excess weight are highly prevalent in adolescents and young adults, and can contribute to the development of NCDs and premature mortality in the adult. Objective: Estimate the magnitude and factors associated with risk behaviors for NCDs in adolescents and young adults in Brazil. Methods: Cross-sectional, baseline study population, which used as a data source the National Health Survey conducted in 2019. The population analyzed were teenagers and young people aged 15 to 24. The data were collected through individual interviews during home visits, through a standardized form. The dependent variables included the main risk factors for Chronic Noncommunicable Diseases (NCDs). The demographic variables and socioeconomic variables were used as independent. Multiple regression models Poisson were applied to investigate the magnitude of the association between the independent variables and the dependent variables. The PNS 2019 was approved by the National Ethics Commission in Research (opinion: 3,529,376). Results: 10,460 individuals (5,001 men and 5,459 women). Regardless of gender, the most common risk factors prevalent were the nonrecommended consumption of fruits and vegetables (92.6%) and physical inactivity during leisure time (43.3%). The prevalence of tobacco smokers, consumption of alcoholic drinks once or more a month and alcohol abuse were 8.9%, 28.7%, 18.5%, respectively. The prevalence of regular consumption of soft drinks and/or artificial juices was 17.2%. The prevalence of excess weight was 32.5%. Compared to women, men had a higher prevalence of smoking, consumption of alcoholic beverages once or more a month, abusive consumption of alcoholic beverages, insufficient consumption of fruits and vegetables and consumption of ultra-processed. On the other hand, women had a higher prevalence of physical inactivity during leisure time and being overweight. Young adults, males and individuals with less education, of black race/color, with lower family income and Residents of urban areas had a higher prevalence for most risk factors. risk. Conclusions: There was a high prevalence of risk factors in adolescents and young Brazilian adults, mainly among young men and women individuals with less education, of black race/color, with lower family income and residents of urban areas. These results indicate the need for policies to reduction in the magnitude of risk factors for NCDs in adolescents and young adults in Brazil. Relevance and impact: This is the first comprehensive study that estimated the prevalence and factors associated with risk behaviors in adolescents and adults young people, including the non-student population. The results of the study can support specific actions for this population within the Strategic Action Plan for the Coping with Chronic Diseases and Non-Communicable Diseases in Brazil 2021-2030 of the Ministry of Health, including intensification of health promotion actions and disease prevention in subpopulations with a higher prevalence of risk factors.
Caracterização epidemiológica e genômica de amostras de rotavírus humano espécie A em Goiânia-Goiás
(Universidade Federal de Goiás, 2016-09-22) Almeida, Tâmera Nunes Vieira; Cardoso, Divina das Dôres de Paula; http://lattes.cnpq.br/9770835116155857; Cardoso, Divina das Dôres de Paula; Soares, Célia Maria de Almeida; Mascarenhas, Joana D'Arc Pereira; Telles, Mariana Pires de Campos; Martins, Regina Maria Bringel
Rotavirus A (RVA) is an important causative agent of acute gastroenteritis (AGE), and vaccination is recommended for the prevention and control of this virus. In Brazil, since 2006, two vaccines have been used, with Rotarix® included in the National Immunization Program. Since its implementation, there has been a reduction in hospitalization rates and positivity for RVA. In this sense, the present study aimed to detect RVA from stool samples from children up to five years of age, with or without GEA, obtained in the period 2014-2015, in addition to characterizing the 11 genomic segments of RVA of samples obtained in pre- and post-vaccine periods and compare them to the vaccine sample. 341 stool samples were analyzed, 335 obtained in the period 2014-2015 and six archival samples positive for RVA, one from the pre-vaccine period. RVA detection was performed by polyacrylamide gel electrophoresis and G (VP7) and P (VP4) genotyping by Mulitplex-Nested-PCR. The 11 genomic segments were characterized by sequencing and molecular modeling was done for VP7 and VP4. Of the 335 stool samples (2014-2015), nine were positive for RVA with a long electropherotypic pattern, four of which were characterized as G12P[8]. Of the six archive samples, also a long standard, five were G1P[8], one of which was from the pre-vaccine period. The characterization of the 11 genomic segments was possible for three samples, two archive samples (G1P[8]), one from the pre-vaccine period and the other (G12P[8]) from the 2014-2015 period. The three samples were characterized as genogroup I. Phylogenetic analysis made it possible to differentiate lineages for VP7, VP4, VP6 and NSP4; samples G1, from the pre- and post-vaccine periods, were characterized as lineages II and I, respectively, and G12, as lineage III, and samples P[8] as lineage III. Samples I1 (VP6) were characterized as lineage IV (pre-vaccine) and I (post-vaccine) and samples E1 (NSP4) were characterized as lineage III. High nucleotide and amino acid identity was verified for the 11 genomic segments of the three samples in relation to the vaccine, being lower for VP7 and VP4 of the G12 sample P[8]. This lesser identity was evident in the protein structure, mainly in the antigenic epitopes of both proteins. In conclusion, RVA continues to circulate with the same genotype as the vaccines and with a different genotype, which reinforces the need for continuous monitoring of the agent in the context of vaccination.
Estudo epidemiológico e molecular da variante Omicron do SARS-CoV-2 no Estado do Tocantins
(Universidade Federal de Goiás, 2024-06-25) Santos, Mateus Silva; Souza, Ueric José Borges de; http://lattes.cnpq.br/6340952274603852; Soares, Celia Maria de Almeida; http://lattes.cnpq.br/8539946335852637; Soares, Celia Maria de Almeida; Bailão, Alexandre Melo; Souza, Menira Borges de Lima dias e; Oliveira, Lucas Nojosa; D’Alessandro, Walmirton Bezerra
Introduction: SARS-CoV-2 infection associated with COVID-19 is one of the greatest global public health challenges, contributing to high morbidity and mortality in different age groups, with some population segments being more affected. The emergence of new variants of the SARS-CoV-2 virus, such as Omicron, is a reflection of selective advantage, translated as greater transmissibility and the ability to replicate in people previously exposed to the virus. In Brazil, the variant was very prominent, even when the numbers of immunized individuals were already high. Therefore, this research aims to promote an epidemiological and molecular study on the Omicron variant of SARS-CoV-2 in the state of Tocantins. Methods: This is an analytical cross-sectional study with a quantitative approach, conducted using SARS-CoV-2 positive samples from the Central Laboratory of Public Health of Tocantins (LACEN-TO). The samples were sequenced and taken to experiments in order to verify the quality of the sequencing, detect possible mutations and identify the main variants of concern. Subsequently, phylogenetic analysis was performed in order to observe the degree of dispersion of the most predominant variant in the state of Tocantins. Results: In the present study, 556 samples positive for the Omicron variant of SARS-CoV-2 were used. Among the results, it was observed that the state of Tocantins presented, during the study period, about 39 lineages of the Omicron variant, some of which were associated with a higher transmissibility rate. The biggest highlight was the XBB.1.18.1 and XBB.1.5 subvariants, being one of the main circulating in Tocantins in 2023. Phylogenetic analyses suggest that the state may have contributed to the dispersion of the subvariants not only in Brazil but also in the world. Conclusions: The results of the present study showed a high prevalence of the Omicron variant in Tocantins between December 2021 and June 2023, in addition to showing that the state may have contributed to the spread of the XBB.1.18.1 subvariant in Brazil. Relevance and impact: It is worth noting that due to the high frequency of mutations of the Omicron variant of SARS-CoV-2, surveillance is necessary to identify possible new entries of the virus not only in the northern Brazilian state but also throughout the country.
Avaliação da resposta imune celular a antígenos recombinantes do Mycobacterium leprae e potencial aplicação para o diagnóstico da hanseníase paucibacilar
(Universidade Federal de Goiás, 2011-06-30) Sampaio, Lucas Henrique Ferreira; Stefani, Mariane Martins de Araújo; http://lattes.cnpq.br/5581414958714905; Stefani, Mariane Martins de Araújo; Grossi, Maria Aparecida Faria; Moraes, Mílton Osório; Kipinis, Ana Paula Junqueira; Araújo Filho, João Alves de
Title: The evaluation of cellular immune responses to Mycobacterium leprae recombinant antigens and potential application for the diagnosis of paucibacillary leprosy. Introduction: Leprosy is a chronic and debilitating infectious disease that is characterized by a spectrum of dermato-neurological manifestations associated with different patterns of immune responses. At one end of the spectrum paucibacillary patients (PB) which include tuberculoid (TT) and borderline tuberculoid (BT) patients mount a strong cellular immune response. On the extreme multibacillary (MB) patients including borderline-borderline (BB), borderline-lepromatous (BL) and lepromatous (LL) forms, respond to infection with vigorous antibody production. The diagnosis of leprosy is based on clinical manifestations hampering the early diagnosis before the onset of sequelae. The development laboratory tests applicable for early leprosy diagnosis is considered essential to reduce possible sources of transmission and the number of patients with physical disabilities. Methods: This work investigated the immune reactivity of a panel of 41 M. leprae (ML) recombinant proteins. The immune reactivity to ML proteins was evaluated by the production of IFNy, measured by ELISA, in the supernatants of 24 hours cultures of heparinized whole blood (whole blood assays/WBA) stimulated with ML antigen (10ug/ml). Study groups were leprosy patients both PB (TT / BT) and MB (BL / LL), newly diagnosed, untreated, classified according to Ridley and Jopling criteria. Household contacts of MB patients (HHC), HIV-1 negative patients with pulmonary tuberculosis (TB) and healthy individuals from the same endemic area (EC) were also investigated. In silico predictions were used to investigate the level of identity of the ML proteins with counterparts in other mycobacteria and to assesse the presence of potential T cell epitopes. For a selected group of immunogenic and specific ML antigens, the profile of 14 cytokines/chemokines induced in WBA was also investigated by Multiplex plataform. Results and Conclusions: The WBA results identified 11 out of 41 M. leprae recombinant proteins (ML0405, ML2055, ML2331, ML0840, ML1623, ML1556, MLI632, ML1685, ML0276, ML2044, 46f) that were classified as immunogenic and capable of inducing specific cellular immune response. These ML antigens were considered to have potential application for the development of laboratory tests for the diagnosis of PB leprosy. The same pattern of immunoreactivity identified among PB leprosy patients was observed among HHC, while MB leprosy, TB patients and healthy individuals did not respond to these antigens. In silico predictions of immunogenicity and specificity were not confirmed by ex vivo WBA results. The multiplex cytokine study with a selected group of ML antigens showed that besides IFNy, patients with PB leprosy produce other cytokines characteristic of Th1 cells (IL-2 and IL-12). Nevertheless these results that IFNy remained the best immunological marker of cellular immune response of PB patients to recombinant M. leprae proteins. MB leprosy patients secrete mainly Th2 type cytokines such as IL-4 and IL-5 in response to recombinant ML proteins. None of the 14 cytokines/chemokines analyzed in the multiplex was able to distinguish the cellular immune responses of PB patients from the majority of HHC. Although the majority of HHC response identically to PB, we observed that some individuals at greater risk of leprosy infection can mount a Th2 response, similar to MB patients.
Associação entre tipos específicos de HPV e carga viral com a gravidade da neoplasia cervical
(Universidade Federal de Goiás, 2012-12-20) Guimarães, Narriman Kennia da Silva Barros; Santos, Silvia Helena Rabelo do; http://lattes.cnpq.br/4994826511439492; Santos, Silvia Helena rabelo dos; Miranda, Angélica Espinosa; Val, Isabel Cristina Chulvis do; Souza, Menira Borges de Lima Dias e; Lino Júnior, Ruy de Souza
Introduction: Cervical cancer is a rare consequence and developed long term from a infection by specific types of human papillomavirus (HPV). There are factors related to the acquisition of infection and its persistence that increase the risk of developing cervical neoplasia. The type-specific viral infection and higher viral loads values appear to be related to persistence of virus and progression of neoplasia and therefore with the severity of cervical neoplasia. Objectives: To identify the specific types of HPV in different age groups as well as the importance of viral load of HPV 16 with the severity of cervical neoplasia. Methods: This cross-sectional study conducted in Goiânia, Goiás, included women referred to the Hospitals Santa Casa de Misericórdia de Goiânia and Hospital Mother and Child, by presenting changes in routine cytological examination. HPV DNA was detected by polymerase chain reaction (PCR) and HPV genotyping was performed by reverse hybridization assay. A total of 331 women with cytological diagnosis were selected, 238 of them with histological diagnosis. After PCR for HPV, 58 women were excluded for being HPV negative. In the 273 HPV-positive women an analysis of the association between HPV types and risk of severity of cytological diagnosis by age group was carried out in the following categorization: <30 years, 30-39 years, 40-49 years and ≥ 50 years. To evaluate the association between viral load values with severity of cytological and histological diagnosis, 77 women HPV 16 positive by PCR in real time were selected. Results: The overall prevalence of HPV infection was 82.5%. HPV 16 was the most prevalent type representing 44.7% of cases. Infections by HPV 16 and / or 18 were significantly associated with both the cytological diagnosis of HSIL or more severe lesions (OR: 2.12 95% CI 0.98 to 4.59) and either with the histological diagnosis of CIN 2 or more severe (OR: 3.21 95% CI 1.21 to 8.59) lesions in women younger than 30 years. The cytological diagnosis of HSIL or more severe lesions (OR 4.59, 95% CI: 1.4 to 15.49, p = 0.004) and histological diagnosis of high-grade neoplasia (≥ CIN 2) (OR 6.51; 95% CI: 2.9 to 20.92, p = 0.0002) were significantly associated with higher viral load values in women infected with HPV 16. Conclusions: These results support the hypothesis that infection with HPV 16 and / or 18 in young women can quickly lead to the formation of more severe lesions and high viral loads resulting from infection by HPV 16 are associated with the severity of cervical neoplasia.
Análise molecular e de qualidade de vida dos pacientes e familiares com xeroderma pigmentosum, residentes em Goiás, Brasil
(Universidade Federal de Goiás, 2016-03-07) Souto, Rafael; Siqueira Júnior, João Bosco; http://lattes.cnpq.br/3644529827602550; Menck, Carlos Frederico Martins; https://orcid.org/0000-0003-1941-0694; Menck, Carlos Frederico Martins; Lacerda, Elisângela de Paula Silveira; Vêncio, Eneida Franco; Teles, Sheila Araújo; Brasil, Virginia Visconde
Xeroderma pigmentosum (XP) variant is an autosomal recessive disease that involves changes in POLH. The study aimed to characterize the distribution of alleles mutated by Real Time PCR (RT-qPCR) in patients and families with clinical suspicion of XP, residents in Araras/Faina, State of Goiás. Additionally, we also, planned to evaluate the quality of life (QoL) by WHOQOL-Bref. In this community, the skin cancer incidence, due to this syndrome, is caused by mutation in the POLH gene, which encodes for DNA, polymerase eta, and two distinct mutations were detected, at the intron 6 e exon 8. Morover, at Trindade a different mutation was found in the same gene (intron 10). Molecular analysis by Real Time PCR (RT-qPCR) o 125 individuals at-tempted to identify the mutated alleles in POLH, which can result in disease and impact on quality of life. Of these, 29 clinically diagnosed as affected by XP syndrome, and 18 in the community of Araras/Faina and 11 are from other Goiás State locations. In Araras/Faina, of the 114 individuals analyzed, 12 were homozygous for the mutanted allele at the beginning of intron 6 (XPV 6/6), one homozygous for the mutanted allele at exon 8 (XPV8/8) and 5 are compound heterozygous for compounds two alleles (XPV 6/8). In addition, 36 patients were identified as carrying (as heterozygous) the mutation at intron 6 (XPV 6/wild-tipe) 12 carriers for muta-tion at exon 8 (8 XPV/wild-type) and 48 participants were wild type for the two alleles (XPV wild type/wild). In the study of 11 clinically affected patients and residents in other regions of the state of Goiás, 2 were positive for XPV with mutations in intron 10 (XPV 10/10) and 9 were negative for the three alleles identified in XPV. The Quality of Life evaluation gave relatively high scores when compared to the work of other groups that studied the Tourette syndrome, Wilson's disease and Thalassemia Major. In comparison using the Student t test between QoL scores of patients by XPV and not sick, it was obtained a p ≤ 0.05 for all domains of the WHOQOL-Bref, demonstrating that the XPV impacts the quality of life of those affected. However, even in a more stratified analysis , the comparison between QoL scores and genotypes for XPV, obtained a p ≤ 0.05 for the Physical and Environmental domains. Thus, we believe that molecular tests come uncovering cases of XP that were underreported showing the actual frequency of the syndrome in the state of Goiás, in addition, the measure of the perceived quality of life is showing the impact that these mutations promote affected in the XPV.
Identificação por imunoproteômica dos exoantígenos do complexo paracoccidioides, com potencial aplicação no diagnóstico e terapia da paracoccidioidomicose
(Universidade Federal de Goiás, 2019-08-26) Moreira, André Luís Elias; Bailão, Alexandre Melo; http://lattes.cnpq.br/5415221996976886; Bailão, Alexandre Melo; Borges, Clayton Luiz; Silva Neto, Benedito Rodrigues da; Rocha, Thiago Lopes; Oliveira, Milton Adriano Pelli de
Identification by immunoproteomic of exoantigens of the Paracoccidioides complex, with potential application in diagnosis and therapy of Paracoccidioidomycosis Fungi of Paracoccidioides complex are the etiological agents of Paracoccidioidomycosis (PCM), a systemic mycosis restricted to Latin American countries. Currently, the Paracoccidioides genus is represented by P. lutzii, P. americana, P. brasiliensis, P. restrepiensis and P. venezuelensis. In some cases, oral and skin mucosal lesions caused by other pathogens may coincide with lesions caused by Paracoccidioides spp.. Moreover, even with the advances in immunological techniques used for the diagnosis of fungal diseases, false-positive results rates for PCM are present. Thus, we investigated which antigens are secreted by 4 species of the Paracoccidioides complex in order to identify and characterize new molecules, thus increasing the spectrum of antigens to be used for future diagnostic tests of PCM. Through of nanoUPLC-MSE, 79 exoantigens were identified in 4 Paracoccidioides species. In silico analysis revealed 2 exoantigens exclusive to P. lutzii species, as well as the identification of 44 unique B-cell epitopes of the Paracoccidioides complex. Thirteen exclusive epitopes distributed among Paracoccidioides species also predicted, being this excellent molecules to be employed in the future for epidemiological studies. These results demonstrate a range of epitopes exclusive to the Paracoccidioides complex as well as the identification of molecules unique to each fungal species. In addition, these analyzes allowed the identification of new candidate biomarkers to PCM diagnosis, as well as the identification of molecules to be used as future epidemiological biomarkers.
Carga epidemiológica da coqueluche e avaliação de impacto de vacinação de gestantes contra coqueluche implementada no Brasil em 2014
(Universidade Federal de Goiás, 2022-08-10) Bagattini, Ângela Maria; Toscano, Cristiana Maria; http://lattes.cnpq.br/3772312631884265; Toscano, Cristiana Maria; Morais Neto, Otaliba Libânio de; Siqueira Júnior, João Bosco; Silva, Lara Lívia Santos da; Kuchenbecker, Ricardo de Souza
Introduction: Pertussis is an acute infectious disease of respiratory transmission, with cyclical occurrence, it is endemic worldwide, represents an important global burden, particularly in children under one year of age who have more severe conditions and may progress to death. Between 2010 and 2014, a sudden and atypical increase in the number of cases of the disease was observed in several countries, including Brazil. There are several hypotheses about the factors associated with this resurgence, including disease cyclicality, replacement of whole-cell vaccines with acellular vaccines, falling vaccine coverage in children, and the effectiveness and duration of protection of vaccines in children, among others. Objectives: This study aims to characterize and estimate the epidemiological situation of pertussis in Brazil, evaluate the impact of vaccination of pregnant women with pertussis vaccine (dTpa) implemented in Brazil in 2014. Also, review the evidence about protection and duration of protection conferred by the whole cell vaccine against pertussis used for vaccination of children in the National Programs of Immunization. Methods: A study in three stages was carried out. The first stage described the epidemiological situation of whooping cough in morbidity and mortality in Brazil from 2000 to 2016. Next, the second stage with an interrupted time series ecological study was carried out with data adjusted by month and using the ARIMA model to assess the impact on cases and hospitalizations of children under five years of age with the introduction of the dTpa vaccine for pregnant women in 2014. The two stages used three independent health information systems, the Information System for Notifiable Diseases (SINAN), the Hospital Information System (SIH), the Mortality Information System (SIM) and the National Immunization Program Information System (SI-PNI), data were aggregated and evaluated by age group and federation unit. The third stage of the study was carried out through a systematic review to assess the effectiveness and duration of protection provided by the whole cell pertussis vaccine (DTPw) in children considering the vaccines currently available on the international market. Results: Pertussis showed cyclical patterns of disease burden over time between 2000 and 2016 in Brazil, in different regions with heterogeneous conditions, with a well-defined outbreak that started in 2011 and peaked in 2014, reaching mainly and more severely. children under six months, with 20,103 (54%), 19,919 hospitalizations (79%) and 565 deaths (93%). The incorporation of dTpa vaccination in pregnant women was associated with a significant reduction in pertussis cases and hospitalizations in children under six months of age when coverage is above 45%. After the introduction of dTpa, it is estimated that 2,124 cases and 1,439 hospitalizations for pertussis were avoided in children under six months of age in states with coverage above 45% between 2015 and 2016. Additionally, 12 studies with DTwP conducted between 2007 and 2020 were included for review, which have varied methodological quality and lack evidence on immunogenicity and duration of immunity indicating a short duration, less than five years. Conclusions: The analysis of different health information systems used showed consistent results throughout the period analyzed, reflecting the cyclicity of the disease and its resurgence from 2011. The incorporation of dTpa vaccination in pregnant women resulted in an impact on the reduction of hospitalizations and deaths of children when vaccination coverage above 45% is achieved. The wP vaccines currently in use have scant evidence of duration of immunity, even though they are used in over 100 countries, in most low- and middle-income countries. Relevance and Impact: The results of this work reinforce the importance of achieving and maintaining dTpa vaccination coverage in pregnant women above 45% in order to obtain a significant impact of vaccination of pregnant women in reducing hospitalizations for pertussis in children. Although wP is one of the most used vaccines globally in children in immunization programs in low- and middle-income countries, there has been an important change in the producers of these vaccines in recent decades, with large pharmaceutical companies having left the market and being replaced by producers in countries emerging technologies that today account for the totality of wP vaccines produced and used in the world. Evidence suggests that the duration of protection afforded by these vaccines in children is short. However, better quality evidence on the effectiveness and duration of immunity conferred by these vaccines is needed to support the definition of more appropriate vaccination strategies.
Tendência da mortalidade por pneumonia em idosos no Brasil e o contexto da vacinação pneumocócica
(Universidade Federal de Goiás, 2019-06-12) Miranda, Denismar Borges de; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Morais Neto, Otaliba Libânio de; http://lattes.cnpq.br/4030124246791320; Moraes Neto, Otaliba Libânio de; Turchi, Marília Dalva; Souza, Maria de Fátima Marinho de; Bierrenbach, Ana Luiza; Sartori, Ana Lúcia
Community-acquired pneumonia is one of the most common infectious diseases and is considered a major cause of morbidity and mortality in the elderly population worldwide. Studies show the direct and indirect impact of 10-valent pneumococcal vaccine on hospitalizations for pneumonia in several countries. There is scarce knowledge regarding this impact on mortality in the elderly in the world and, to date, no evidence in the Brazilian population. This study aimed to propose models for correcting mortality rates due to pneumonia in the elderly in Brazil and to evaluate the indirect impact of PCV-10, introduced in the childhood immunization schedule, at these rates. This is a time-series study of mortality rates from pneumonia in the elderly from 2005 to 2016. For the time-series analysis, the models for predicting pneumonia rates, if the vaccine had not been implemented, were Seasonal Autoregressive Integrated Moving Average (SARIMA) in the presence of seasonality, Auto Regressive Integrated Moving Averages (ARIMA) when there was only trend, and Autoregressive Moving Average (ARMA) in the absence of trend and seasonality. Percentage difference between observed and predicted rates were calculated, considering statistical significance of 5%. There was an increasing trend of mortality due to pneumonia in the elderly in Brazil. Interrupted time series analysis showed that the estimated pneumonia mortality rates from the study were significantly lower than those predicted by the analysis models. There was probably an indirect impact of PCV-10 on the elderly. In the Southeast region there was a statistically significant difference between the rates observed and the predicted in the three age groups of the elderly.
Epidemiologia molecular de isolados de toxoplasma Gondii na região metropolitana de Goiânia, Goiás, Brasil
(Universidade Federal de Goiás, 2018-01-12) Rezende, Hanstter Hallison Alves; Vinaud, Marina Clare; http://lattes.cnpq.br/1921551651088660; Castro, Ana Maria de; http://lattes.cnpq.br/9232309971000621; Castro, Ana Maria de; Fernandes, Everton Kort Kamp; Rocha, Thiago Lopes; Cardoso, Cléver Gomes; Soave, Danilo Figueiredo
The protozoan Toxoplasma gondii is the etiological agent of toxoplasmosis and its definitive hosts are domestic cats (Felis catus) and other wild felids. Within the cities, stray cats are responsible for the dissemination of the parasite in the environment as they release oocysts which are the infective forms for humans and other animals. Backyard chickens (Gallus gallus) are in constant contact with the environment and feed directly from the soil. Therefore they are important indicators of environmental conditions. The knowledge regarding prevalence, biological and genetic characteristics of T. gondii are of utmost importance for the comprehension of the complex host-parasite relationship. Thus the aim of this study was to evaluate the concordance of laboratory techniques used to detect the parasite; to determine the prevalence, biology and molecular epidemiology of T. gondii isolated from stray cats and backyard chickens from the metropolitan region of Goiania, in order to better comprehend the infection. This is the first performed study to determine the genetic and biologic characterization of T. gondii in the state of Goias. This study used 24 stray cats captured by the Center for the Zoonosis Control in Goiania and 50 backyard chickens from the Metropolitan Region of Goiania, Goias. The serologic triage was performed by IHA and showed positivity of 87.4% (21/24) cats and 96% (48/50) backyard chickens for T. gondii. The bioassay was performed using the brain and hearts of the cats and chickens obtained after euthanasia of the animals. After the peptic digestion the homogenate tissues was intraperitoneally inoculated in groups of three Swiss mice each which were daily observed in order to detect signs of acute toxoplasmosis. The asymptomatic mice were euthanized after 60 days followed by serologic analysis through indirect immunofluorescence. Fragments of brain from these animals were observed under optic microscopy in order to visualize tissue cysts. Part of the homogenate was submitted to DNA extraction and polymerase chain reaction (PCR) in which 75% (18/24) cats and 64% (32/50) backyard chickens were positive. The correlation between IHA and PCR from both animals was considered weak. It was not possible to obtain isolate strains from cats. From the chickens it was possible to obtain 15 isolates strains from which 8 presented tachyzoites (acute toxoplasmosis) and 7 presented brain tissues (chronic toxoplasmosis). After the DNA extraction from the isolates the RFLP-PCR was performed using the following primers SAG1, 5’-3’ SAG2, altSAG, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3. It was possible to define the genotype from 9 isolates. According to ToxoDB seven isolates corresponded to genotype #65 and two isolates have not been described previously. The genetic analysis showed high diversity and variability. The virulence essays showed that the mortality rate in mice in seven isolates that presented tachyzoites, from the same genotype, detected high virulence in 4 isolates and intermediary virulence in 3. The morphometry analysis of the tachyzoites of these isolates showed statistical difference in at least one of the analyzed variables such as length or nuclei-apical complex distance. These phenotypic differences in isolates from the same genotype show the need to the continuity of the genetic characterization of the parasite using other primers which could be related to the isolated phenotype. The study demonstrated the importance of knowledge about the molecular epidemiology of T. gondii in the metropolitan region of Goiânia, which presents high rates of seroprevalence in hosts.
Identificação de biomarcadores para o diagnóstico da toxoplasmose aguda e congênita
(Universidade Federal de Goiás, 2020-11-27) Storchilo, Heloisa Ribeiro; Castro, Ana Maria de; http://lattes.cnpq.br/9232309971000621; Borges, Clayton Luiz; Alves, Daniella de Sousa Mendes Moreira; Rezende, Hanstter Hallison Alves; Paccez, Juliano Domiraci; Castro, Ana Maria de
Introduction: The diagnosis of congenital toxoplasmosis is complex and might take months to confirm since most newborns do not present symptoms and levels of undetected IgM and IgA anti-Toxoplasma gondii antibodies. Besides, pregnant women may have residual IgM, making it difficult to diagnose acute infection during pregnancy. Despite the various serological tests developed, there are few studies about biomarkers that can assist in the diagnosis of acute and congenital toxoplasmosis. Objective: Analyze the immunoreactivity profile of T. gondii protein with the potential to be biomarkers for the diagnosis of acute toxoplasmosis and the diagnosis and prognosis of congenital toxoplasmosis. Methods: Serum samples were selected from children with symptomatic and asymptomatic congenital toxoplasmosis and women of childbearing age or pregnant women with acute and chronic acquired toxoplasmosis. These samples were grouped according to the patients' laboratory and clinical results. Sodium Dodecyl Sulfate - Polyacrylamide Gel Electrophoresis (SDS-PAGE) was used to separate T. gondii proteins. The Immunoblotting technique was applied to the analysis of immunoreactive bands profile by IgG antibodies, using nitrocellulose membranes sensitized with parasite proteins. Results: One hundred and sixteen samples were analyzed. When comparing immunoreactive bands profile for antibodies present in samples from different groups and subgroups, the 150, 18.5, and 16.96 kDa proteins were more immunoreactive by the antibodies present in serum samples from the acquired infection group. The 343, 189, 150, 75, and 42 kDa proteins showed more chance to be detected by the symptomatic congenital infection subgroup, while the 61, 50, and 16.96 kDa proteins were significantly immunoreactive by the acute infection subgroup. Conclusions: Before obtained results, it was possible to identify potential biomarkers that may assist in early diagnosis and treatment of toxoplasmosis, avoiding the appearance of clinical manifestations throughout the life of children congenitally infected.
Identificação de novos fármacos antimaláricos através de estratégia de quimiogenômica por reposicionamento e validação experimental
(Universidade Federal de Goiás, 2018-03-05) Rodrigues, Juliana; Cravo, Pedro Vitor Lemos; http://lattes.cnpq.br/1059199347781390; Andrade, Carolina Horta; Andrade, Carolina Horta; Andrade, Éverton Kort Kamp; Castro, Ana Maria; Neves, Bruno Júnior; Costa, Fabio Trindade Maranhão
Malaria is an infectious disease of possible chronic evolution that affects billions of people in the tropics and subtropics. P. falciparum is the most lethal malaria parasite of humans, while P. vivax is the most widely distributed. The effectiveness of the antimalarial treatment is compromised by the ability of the parasite to evolve resistance to the compounds and by the lack of new effective antimalarials, underscoring the urgent need for the discovery of new drugs. One of the strategies that has been gradually explored in the search for new therapies is the so-called "drug repurposing" approach. In this context, the goal of the present study was to use a drug repurposing-chemogenomics strategy to identify effective drugs against malaria parasites. A comparative genomics tool available from the TDR Targets Database was used through to select targets expected to be present exclusively in P. falciparum and P. vivax parasites, but absent in humans. Each of the selected targets was then used as a query in the following databases: Drugbank, Therapeutic Target Database and STITCH. The P. falciparum and P. vivax targets were aligned with their predicted homologue targets, using pairwise BLAST, to compare functionally relevant regions. Only those where ≥ 80% overlap was observed between the two sequences for the corresponding drug target were considered for subsequent studies. Thereafter, the drugs identified were submitted to a bibliographic search to find drugs that were never evaluated against malaria parasites in the past. A prediction of active compounds was performed through binary QSAR models. The selected drugs were submitted to in vitro assays using asexual stages of P. falciparum (strains 3D7, chloroquine-sensitive, and W2, multidrug-resistant). Epirubicin displayed potent in vitro activity against the 3D7 strain (IC50 = 140 nM). In addition, the drug was shown to be about twice as active against the W2 resistant strain (IC50 = 69 nM), exhibiting even greater activity than chloroquine. At present, in vitro experiments in sexual stages (ookinete conversion) and in vivo assays with P. berghei and P. chabaudi are being carried out. In conclusion, epirubicin is a good antimalarial drug candidate, although future studies are required to investigate its mechanism of action, potential toxicity, and eventually, to advance in the drug development process.
Avaliação da densidade mineral óssea e estimativa de risco de fraturas em homens vivendo com HIV
(Universidade Federal de Goiás, 2018-12-17) Sousa, Clarissa Alencar de; Turchi, Marília Dalva; http://lattes.cnpq.br/3769826743537934; Turchi, Marília Dalva; Siqueira Júnior, João Bosco; Teles, Sheila Araújo; Silva, Nilzio Antonio da; Albuquerque, Maria de Fátima Pessoa Militao de
Evaluation of bone mineral density and fracture risk estimation in men living with HIV. Introduction: HIV carriers are at increased risk of developing chronic noncommunicable diseases at an early age. The reduction of bone mineral density, before the age of 50 years, is described in this population. Few studies evaluate the magnitude of osteoporosis in men with HIV, as well as screening strategies in this segment. Objectives: To estimate the prevalence and to investigate risk factors for changes in bone mineral density (BMD); compare osteoporosis prediction model, with bone-densitometry as the gold standard; to evaluate the risk of fractures using an algorithm in HIV-positive men. Method: Cross-sectional study, population of men with HIV, over 40 years old, using ART, attended in Goiânia-Goiás. Participants answered a standardized questionnaire, performed clinical evaluation and laboratory tests. All investigated bone mineral density through dual energy X-ray absorptiometry (DXA). Osteoporosis was defined as bone mineral density less than / equal to 2.5 standard deviations (SD), considering as a reference a young, healthy population categorized by sex. Osteopenia was defined as a reduction between 1 and 2.4 SD of bone mineral density according to WHO criteria. The Osteoporosis Self-Assessment Tool (which uses weight and age data) was evaluated in the prediction of osteoporosis and Low BMD. A ROC curve was constructed to assess OST performance. Results: The participants' age ranged from 40 to 72 years, with a mean of 49.6 (SD = 7.5). The prevalence of low bone mineral density was 56.8% (95% CI: 49.25-64, 13%) and osteoporosis 16% (95% CI 11.0 - 22.1). The risk of fractures in 10-years ranged from 1.1% to 20%, with a median of 1.9%. The factors associated with bone density reduction were the use of tenofovir disproxil fumarate and low BMI. The osteoporosis prediction instrument (OST) presented values of area under the curve of 0.71 and 0.67 in the prediction of osteoporosis and low bone mineral density. The cutoff point 7 obtained the best performance in predicting osteoporosis. The instrument revealed low to moderate predictive power over low bone mineral density and osteoporosis compared to DXA. Conclusion: There was a high prevalence of BMD reduction and overweight in a population of relatively young men with HIV.
Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
(Universidade Federal de Goiás, 2015-02-23) Fraga, Carolina Miguel; Castro, Ana Maria de; http://lattes.cnpq.br/9232309971000621; Vinaud, Marina Clare; http://lattes.cnpq.br/1921551651088660; Cruz, Aparecido Divino da; Costa, Tatiane Luiza da; Bezerra, José Clecildo Barreto; Fernandes, Éverton Kort Kamp
Human infections caused by Taenia spp may be more frequent than they are reported especially if occurred in immunodepressed patients and if the location of the parasites does not involve vital organs. Albendazole is one of the drugs used in the treatment of such infections and its use in mass treatment campaigns may accelerate the resistance development from the parasites both in humans and animal hosts. The aim of this study was to in vitro evaluate the biochemical alterations in T. crassiceps cysticerci after the treatment with a benzimidazolic derivatice (RCB20). The cysticerci were removed from the peritoneal cavity of BALB/c mice with 30 days of infection, macroscopically classified and harvested into 6 well culture plates. 30 cysticerci from each development stage in each well received 5mL of supplemented RPMI culture medium which contained sulfoxide albendazole (ABZSO) (6,5 μM or 13 μM), or RCB20 (6,5 μM or 13 μM). After 24h of culture the cysticerci were removed from the culture medium and both were frozen in liquid nitrogen. Liquid chromatography of high performance and spectrophotometric analysis were performed. It was possible to observe a difficulty in the secretion of substances by the treated cysticerci due to differences in the concentrations of the products dosed from the vesicular fluid and from the culture medium. This was an effect from the mode of action of the drugs which affects the tubulin formation. Regarding the glycolysis it was possible to observe a gradation increase in the secretion/excretion (S/E) of lactate in the treated groups while there was a decrease of this organic acid in the vesicular fluid. As to the energetic metabolism and the citric acid cycle it was possible to observe its traditional sense functioning due to the detection of alf- ketoglutarate. It was possible an increase in the concentrations of citrate, malate, fumarate and succinate in the treated groups. The alternative pathway of energy production such as beta-oxidation of fatty acids and protein catabolism were detected with an increase in the metabolites from those pathways in the treated groups. Therefore we conclude that in spite of not blocking the glucose uptake the drugs influenced its uptake which lead to the use of alternative pathways of energy production. In spite of more soluble and stable the RCB20 formulation did not present a different biochemical effect than ABZSO.
Avaliação da capacidade da nova linhagem de células dendríticas AP284 responder a diferentes agonistas de TLRs e de induzir uma resposta Th17
(Universidade Federal de Goiás, 2018-11-14) Oliveira, Pollyana Guimarães de; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Fonseca, Simone; Pfrimer, Irmtraut Araci Hoffmann; Campos, Helioswilton Sales de; Lacerda, Elisângela Silveira
Dendritic cells (DCs) are antigen presenting cells (APCs) that belongs a diversify group of cells, being still the main cells that can presents the antigen and activate T lymphocytes by inducing different kinds of cytokine production, which can influence the development of different profiles of lymphocytes. The production of IL-12p70 leads to the Th1 profile differentiation, furthermore the IL-23 production can be important for the establishment and maintenance of Th17 profile. Thus, IL-12 and IL-23 play an important role in the induction or establishment of the adaptive immune response. The aim of the study was characterize the DC AP284 cell line by checking its surface markers, TLRs expression and capacity of response to different TLRs agonists. Besides of that, the production of IL-12p40, IL-12p70, IL-23 and the ability to induce Th1 or Th17 profile were evaluated. AP284 cells have expressed surface molecules compatible with DCs including class II MHC, CD11c and 33D1. After stimulation using different TLRs agonists these cells produced higher amounts of de IL-12p40 and IL-23, but no IL-12p70 production was observed. The IFN-γ addition was not able to induce IL-12p70 production, instead of that an inhibition of the IL-12p40 and IL-23 production were observed. The results have also shown that AP284 cell line is related with the Th17 profile because higher amounts of IL-12p40 and IL-23, but not IL-12p70 were observed, besides of that the results showed an increase in IL-17 levels produced by mice lymph node cells after immunization with Freund’s adjuvant and BCG. Thus, AP284 cells can be important to study the mechanisms of induction and regulation related with the production of IL-12p40 and IL-23 working as a possible tool to study the establishment and maintenance of Th17 cells profile. Moreover, AP284 cells have some similar characteristics among the other immortalized murine DCs, but the AP284 line produces a much higher amount of IL-12p40 than all described cells and is also differentiated among them by the production of IL-23.
Influência da inflamação crônica de baixo grau na susceptibilidade à tuberculose e resposta vacinal em camundongos
(Universidade Federal de Goiás, 2019-10-14) Resende, Danilo Pires de; Kipnis, André; Kipnis, Ana Paula Junqueira; http://lattes.cnpq.br/1252262903952987; Kipnis, Ana Paula Junqueira; Fonseca, Simone Gonçalves da; Cominetti, Cristiane; André, Maria Cláudia Dantas Porfírio Borges; Campos, Helioswilton Sales de
Chronic conditions associated with inflammation, such as obesity (OB), diabetes mellitus (DM) and tuberculosis (TB), are serious public health problems. The OB epidemic is increasing worldwide; and the prevalence of adult obesity nearly doubled between 1980 and 2017. Since DM is associated with diabetes, the prevalence of diabetes also increased over the same period, reaching 9% of the adult population worldwide, totaling 422 million people. Studies have been demonstrating DM as a risk factor for the development of tuberculosis, raising the hypothesis of an association between OB, DM and TB. Circulating monocyte subpopulation proportions have been shown to change during OB, DM, and TB, however no studies have evaluated monocyte subpopulations in severe OB / DM and if there are characteristics that may be associated with increased susceptibility to TB. In the first part of this study we demonstrated, in a cross-sectional study, with individuals with severe OB (BMI over 35kg / m2) with or without OB (DM) (n = 50 individuals per group) that the population did not of monocytes from OBDM individuals presents similar characteristics to monocytes from individuals with active pulmonary TB, and monocytes from OBDM and TB individuals are more susceptible to Mycobacterium tuberculosis (Mtb) infection. This suggests that phenotypic similarity and susceptibility of monocytes may be factors contributing to the association between tuberculosis and obesity. Since monocytes/macrophages change in obesity and these changes interfere with the ability to control Mtb, we decided to assess whether the development of obesity could alter the ability to rescue the specific immune response following M. bovis BCG vaccination. Thus, in the second part of this paper, we evaluated whether obesity interferes with BCG vaccine response by vaccinating young C57BL / 6 mice and inducing obesity by hypercaloric diet and by analyzing the immune response after Mtb challenge. Obesity induced after BCG vaccination did not interfere with TCD4 + IFNγ + lymphocyte rescue after Mtb challenge. However, this response to Mtb has been reduced. These results suggest that vaccination of non-obese animals induces vaccine immune responses that do not change with obesity induced metabolic changes.
Avaliação de receptores similares a toll (tlrs) em monócitos de pacientes com doença de Parkinson
(Universidade Federal de Goiás, 2017-06-02) Rocha Sobrinho, Hermínio Maurício da; Dias, Fátima Ribeiro; http://lattes.cnpq.br/5741031258926403; Dias, Fátima Ribeiro; Silva, Marcos Vinícius da; Cruvinel, Wilson de Melo; Diniz, Denise Sisterolli; Gomes, Rodrigo Saar
Parkinson's disease (PD) is a condition of the central nervous system (CNS), chronic and progressive, resulting from the death of brain dopamine-producing neurons. Genetic and epidemiological studies have highlighted the role of neuroinflammation in the pathophysiology of PD, emphasizing that the process of neuroinflammation is associated with the death of dopaminergic neurons. In peripheral blood or tissues, leukocytes activated by pathogen-associated molecular patterns (PAMP) and / or tissue damage (DAMP), via Toll-like receptors (TLR), produce pro and antiinflammatory mediators whose imbalance can lead to a chronic inflammation. Under physiological conditions, three subpopulations of human peripheral blood monocytes are detected: the classical monocytes (CD14++CD16-), the intermediates (CD14++CD16++) and the non-classical (CD14+CD16+), these cells present phenotypic and functional differences that can influence the characteristics of the immune response against DAMPs or PAMPs. The aim of this study was to compare the peripheral blood leukocyte potential of patients with PD or healthy individuals in the production of cytokines (TNFα and IL-10) after stimulation of these cells with TLR4 (LPS) or TLR2 / 1 (Pam3Cys) agonists, to evaluate the effect of the age of DP patients on the production of cytokines in blood cultures, to investigate the percentage of monocyte subpopulations expressing TLR1, TLR2 and TLR10, to evaluate the influence of TLR10 expression on the biological activity of TLR2 to its agonist in PBMC cultures. Two groups of patients with PD were evaluated (≤ 55 years old and ≥ 65 years old), age-matched with healthy controls (n = 26). 6 h-TNFα production was increased after TLR4 stimulation, mainly in young PD patients, whereas TLR2-induced TNFα and IL-10 levels were decreased in PD patients independent of age (p < 0.05). A reverse correlation between LPS-induced TNFα production and age was observed in PD patients and controls, but TNFα induced by TLR2 agonist was not associated with age of PD patients or controls. TNFα production induced by TLR4 but not by TLR2 was reversely associated with the age at PD onset and disease duration. No associations between UPDRS scores and cytokine levels were detected. A higher percentage of CD14++CD16+ monocyte subpopulation was observed in the blood of patients with PD compared to healthy controls, as well as a higher percentage of monocytes from patients expressing TLR10. The expression of TLR2 and TLR10 in peripheral blood monocytes from PD patients was increased relative to that of healthy controls. The results suggest that the peripheral blood leukocyte response to the TLR2 ligand is reduced in PD and that the elevation of TLR10 expression in monocytes influences inhibiting the biological activity of TLR2 to its agonist as demonstrated in the neutralization experiment of TLR10. In this study, the group of DP patients with the highest severity of the disease, evaluated by the UPDRS scale, had a lower percentage of monocytes expressing TLR10, suggesting the expression of this receptor in peripheral blood leukocytes as a possible prognostic marker for DP. These findings, together, may play an important role in the immunopathology of PD. The study of TLR cell expression in peripheral leukocytes and CNS, intracellular signaling pathways and the production of pro and anti-inflammatory mediators is necessary in order to better clarify the role of TLR in the PD pathogenesis and perhaps for the identification of biomarkers of disease prognosis in the blood PD patients.
Acidentes de trânsito em capitais selecionadas do Brasil: estimativa da magnitude corrigida e fatores associados à gravidade da lesão
(Universidade Federal de Goiás, 2017-08-24) Mandacarú, Polyana Maria Pimenta; Morais Neto, Otaliba Libânio de; http://lattes.cnpq.br/4030124246791320; Morais Neto, Otaliba Libânio de; Duarte, Elisabeth Carmen; Mota, Eduardo Luiz Andrade; Ternes, Yves Mauro Fernandes; Itria, Alexander
Introduction: Middle-and low-income countries currently account for 92% of all road transport fatalities worldwide, with an increasing trend in mortality rates, the opposite of what occurs in high-income countries. Brazil has a high morbidity and mortality burden caused by traffic. However, one of the limitations of the knowledge of the real magnitude of traffic accidents in Brazil is the lack of qualified information about traffic accidents by mode of transportation and the underestimation of the actual number of fatalities and serious injuries. In this way, the qualification of the databases through the relationship of health and traffic records allows improving coverage, coverage and quality of information, as well as enhances the epidemiological analysis of this disease in the population. Objectives: To estimate the magnitude of deaths and severe injuries using a linkage procedure as well as the percentage of correction for health and traffic data sources in the municipalities of Belo Horizonte, Campo Grande, Curitiba, Palmas, Teresina and Goiania, and to characterize the factors Associated with deaths and serious injuries in Goiania. Method: Two cross-sectional studies were conducted, using a database of traffic victims (VIT), the Hospital Inpatient System (SIH), and the Mortality Information System (SIM). The first in Belo Horizonte, Campo Grande, Curitiba, Palmas and Teresina and the second in Goiania. A linkage procedure was performed in both studies through the RECLINK III program, identifying true pairs with calculation of the percentage of correction of the underlying cause of death, secondary diagnosis or classification of the victim in the traffic database. In the second study, for the definition of the associated factors for deaths and severe injuries, the incidence ratios with a 95% confidence interval were estimated. The comparison of the incidences between the categories of each variable using bivariate and multivariable regression model using the Poisson regression, with robust variance. Results: The results showed that there was a considerable correction of the basic cause of death, diagnosis of hospitalization or classification of the severity of the victim's injury in traffic records in the six capitals. For SIM, the percentage of correction of the underlying cause of death was 29.9%, 11.9%, 4.2%, 33.5%, and 43.9% for Belo Horizonte, Campo Grande, Curitiba, Teresina and Goiania, respectively. For SIH, the percentage of correction of the secondary diagnosis of hospitalization was 51.3% for Goiania, 24.4% for Belo Horizonte, 96.9% for Campo Grande, 100.0% for Palmas and 33.2% for Teresina. For VIT, there was a change in the classification of the severity of the victim (not severe to severe), with correction percentage of 100.0% for Belo Horizonte and Teresina, 48.0% for Campo Grande, 52.8% for Goiania and 51.4% For Palmas. In the case of nonfatal to fatal, the correction was 29.5%, 52.3%, 74.3%, 4.4% and 72.9%, respectively, for Belo Horizonte, Campo Grande, Curitiba, Palmas and Teresina. For Goiania, the contribution of the linkage procedure to the database of victims was the identification of 15 deaths (9.6%), not classified as such in the transit data base. In Goiania, 70% of all victims were males and 43.7% of all victims were aged between 18 and 29 years and 63% of all accidents were motorcycle occupants. The main factors associated with death were: age over 40 years (40-49 years: RI 2.75, IC 1.11-6.79, 50-59 years: RI 4.46, IC 1.8- 11.04 and 60 and more: RI 7.69, IC 3.15-18-78) bicycle occupants (RI 2.26 IC 1.19-4.3) and pedestrians (RI 2.12 IC 1.26 -3.58) and the occurrence of the accident between 0-6 hours (RI 2.47 IC 1.36-4.47); For the severely injured were: the age group over 40 years (40-49 years: RI 1.62, IC 1.26-2.08, 50-59 years: RI 1.48, IC 1.23-2, 16 and 60 and more: RI 2.00, IC 1.50-2.66), occupants of Motorcycle (RI 2.38 IC 2.01-2.83), Bicycle (RI 2.35 IC 1.76- And the occurrence of the accident between the periods of 00: 00-17: 59 hours (00:00 to 05:59 RI 1, 38 IC 1.1-1.73.06.06 at 11.59 RI 0.72 IC 0.63-0.83; 12:00 at 17.59 RI 0.84 IC 0.73-0.95). Conclusion: The study contributed to the qualification of the coverage and quality of the information of the health and traffic data banks, as well as identified gaps and limitations in the information system that registers ATT.
Genomas completos e parciais de formas recombinantes BF1 e BC do HIV-1 circulantes nos estados de Goiás, Mato Grosso, Mato Grosso do Sul, Tocantins, Maranhão e Piauí
(Universidade Federal de Goiás, 2017-08-14) Reis, Mônica Nogueira da Guarda; Guimarães, Monick Lindenmeyer; http://lattes.cnpq.br/0776265935831372; Stefani, Mariane Martins de Araújo; http://lattes.cnpq.br/5581414958714905; Stefani, Mariane Martins de Araújo; Santos, André Felipe Andrade; Delatorre, Edson Oliveira; Araújo Filho, João Alves de; Cardoso, Ludimila de Paula Vaz
Background and objectives: One of the most striking features of HIV-1 is its extensive genetic polymorphism which allows its classification into four groups (M, N, O and P). The pandemic group M can be classified into nine subtypes (A-D, F-H, J, K), six sub-subtypes (A1-A4, F1-F2), dozens of circulating recombinant forms (CRFs) and countless unique recombinant forms. The molecular epidemiology of HIV-1 in Brazil is complex and dynamic and has been characterized by the cocirculation of subtypes B, F1 and C and BF, BC, BFC and CF recombinants. Previous studies on pol sequences of HIV-1 isolates from six Brazilian States (Goiás, Mato Grosso, Mato Grosso do Sul, Tocantins, Maranhão e Piauí) have shown great variability of BF, BC and FC recombinant viruses. This thesis describes the molecular characterization of these mosaic genomes including reclassification in pol and generation of full length/near full length/ partial genomes of representative isolates. The results of this thesis are presented as articles, one of them is already published and two other are presented as manuscripts to be submitted. Methods: Proviral DNA was extracted from whole blood and four overlapping fragments that compose HIV-1 whole genome were amplified by “nested”-PCR. The generated sequences were aligned (BioEdit 7.2.0) and phylogenetic analysis performed (MEGA 6, Neighbor-Joining, Kimura 2 parameters). The recombination profiles were identified by point analysis, phylogenetic analysis of fragments, and Bootscan analysis (SIMPLOT v3.5.1). The time of the most recent common ancestor (TMRCA) of HIV-1 BF clades was estimated (Bayesian Markov Chain Monte Carlo, BEAST v1.8). Results: Article 1/Plos One: Among 828 HIV-1 isolates from six Brazilian States, phylogenetic analysis of pol identified 87 BF recombinant isolates: 48% (42/87) grouped into five different clusters (Cluster #1-5), 21% (18/87) was CRF_BF-like and 31% (27/87) were classified as URFs_BF. Among 22 isolates that composed the largest BF cluster (#5), we have obtained six full length genomes, one near full length genome and four partial genomes. These 11 isolates, obtained from patients that did not have any epidemiological link shared identical recombination profile in their genomes, allowing the description of a new CRF. This recombinant named CRF90_BF1 is circulating in Goiás, Mato Grosso e Tocantins states. Among 20 BF isolates from the other four clusters we have obtained: three full length genomes, four near full length genomes and five partial genomes. Analysis of these sequences characterized three URFs (Clusters #1, #2 e #3), circulating in the Central West region. The estimated TMRCA for these BF clades was the beginning of the 90’s. BLAST search analysis identified other sequences sharing the same recombination pattern among isolates from the North and South regions, suggesting that they may represent other potential, unidentified CRFs. A moderate rate of CRF28/CRF29_BF-like isolates was seen (16.1%, 14/87) in Goiás, Mato Grosso and Mato Grosso do Sul states. Manuscripts 1 and 2: BC and BF recombinant isolates were also detected (2.9%; 24/828): BC (2,3%, 19/828), BFC (0,4%, 3/828) and CF (0,2%, 2/828). Among these 24 isolates, 19 grouped into six clusters while five (BRGO4156, BRMT2509, BRMT3086, BRMS43, BRPI34) did not cluster. Six clusters were identified (Clusters #1-6): two clusters contained 7 isolates with recombination profiles similar to already identified CRFs_BC (29.2%, 7/24). Cluster #4/CRF31_BC-like comprised 5 isolates (20.8%) and two isolates were Cluster #5/CRF60_BC-like (8.3%). Most patients infected with BC and FC isolates was antirretroviral naïve and (23/24) and 21.7% (5/23) had mutations associated with transmitted drug resistance. Conclusions: Our analyses of isolates from Central West, North and Northeast regions allowed the characterization of the new CRF90_BF1 and different URFs_BF and BC from already described ones. Also isolates sharing recombination profiles with already described ones were also observed (CRF28/29_BF-like, CRF31_BC-like, CRF60_BC-like). Altogether our results indicate that coinfection/ superinfection and intersubtype recombination may be more prevalente that reported. Also, our results indicat the continuing generation of recombinants in the Brazilian epidemic that is taking place in urban centers located away from the epicenter of the epidemic. Continued surveillance studies including full/near full genomes in larger sample sizes are necessary to identify emerging and disseminating recombinants and their implication in the transmission and control of HIV-1 in Brazil.
Identificação de novos compostos bioativos contra tripanossomatídeos a partir de estratégias integradas em química medicinal
(Universidade Federal de Goiás, 2018-04-02) Melo Filho, Cleber Camilo de; Braga, Rodolpho de Campos; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4731114E4; Andrade, Carolina Horta; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4745602P1; Andrade, Carolina Horta; Castro, Ana Maria de; Oliveira, Milton Adriano Pelli de; Lacerda, Elisângela de Paula Silveira; Scotti, Marcus Tullius
Trypanosomatids are parasites that cause different diseases affecting mainly low-income populations from countries in development or underdeveloped countries. These diseases are classified as neglected tropical diseases (NTDs). The few drugs available for the treatment of these parasitic diseases present several problems regarding low efficacy, resistance, and toxicity, making the need of new therapeutic options an urgent task. In this sense, the aim of this work was the identification of novel drug candidates against trypanosomatids through the application of integrated strategies in Medicinal Chemistry. To achieve this goal, three studies were performed combining different computer assisted drug design (CADD) approaches and experimental validation. In the first study, 39 virtual hits were identified by quantitative structure activity relationships (QSAR)-based virtual screening (VS) and selected for experimental evaluation. Among them, 13 compounds were active and selective in vitro against intracellular T. cruzi. Additionally, an in silico multi-parameter analysis for evaluation and comparison of some pharmacokinetic (ADMET) and physicochemical properties, with potency and selectivity, allowed the prioritization of the most promising compounds for further in vivo assays. In the second study, VS was performed for identification of novel potential inhibitors of pyruvate kinase (PK) from Leishmania spp., allowing the discovery of 14 novel potential inhibitors of this enzyme. These compounds were submitted to experimental evaluation against L. infantum amastigotes. In the third study, a dual-target VS was performed, allowing the identification of 15 potential inhibitors of both PK and sterol 14 α-demethylase (CYP51) of Leishmania spp., also predicted as active compounds against L. infantum amastigotes by QSAR models. Therefore, this work has demonstrated the potential of the integration of computational and experimental methods for the identification of active compounds against trypanosomatids.

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