Doutorado em Medicina Tropical e Saúde Pública (IPTSP)
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Item 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 SouzaIntroduction: 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.Item 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 LúciaCommunity-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.Item 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 deIdentification 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.Item 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 FigueiredoThe 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.Item 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 MaranhãoMalaria 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.Item 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 deEvaluation 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.Item 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 ViscondeXeroderma 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.Item 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 deIntroduction: 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.