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Dissertations |
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1
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ALINE DAIANE DOS REIS LIMA
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Evaluation of the Contingency Plan Implementation of the Hospital Universitário de Brasília to face the covid-19 pandemic
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Advisor : MICHELINE MARIE MILWARD DE AZEVEDO MEINERS
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COMMITTEE MEMBERS :
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MICHELINE MARIE MILWARD DE AZEVEDO MEINERS
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ELZA FERREIRA NORONHA
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WILDO NAVEGANTES DE ARAUJO
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ISABEL MARIA RODRIGUES CRAVEIRO
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Data: Feb 10, 2023
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Show Abstract
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Since the public health emergency of international importance due to new coronavirus (covid-19) was established, the government and health institutions in the Federal District have established contingency plans to deal with it, in accordance with the guidelines of the Brazilian health authorities, seeking to guarantee qualified access to victims, prevent its spread and maintain adequate care for people with other health conditions. The objective of the present study was, therefore, to develop the Logical Model and the Analysis and Judgment Matrix to assess the degree of implementation of the Contingency Plan to face covid-19 at the Hospital Universitário de Brasília (HUB- UnB/Ebserh). It is, therefore, an evaluative, observational, quali-quantitative research, carried out in the hospital in a retrospective and prospective way, referring to the period from March 2020 to August 2021. This period comprised the first case of the new coronavirus in the Federal District and the termination of temporary contracts to face the HUB-UnB/Ebserh pandemic. The survey was carried out from July 2020 to November 2022, when the latest data were collected for analysis. The developed and validated Logical Model contains seven dimensions and 18 operations and 109 products (management, assistance, workforce, surveillance, support and strategic inputs, teaching, research and extension, and communication). From the validated indicators, the judgment matrix was structured and validated based on goals provided by the key informants themselves or data found in the literature. The development of evaluation tools for health services, when formulated with the participation of the institution's managers and workers, constitutes a strategy to improve the efficiency of the proposed actions (plans, programs). The products achieved can guide the execution of the plan or actions, define indicators, monitor and evaluate its implementation, as well as point out possible planning weaknesses, enabling its improvement. The participation of managers and workers in the construction of evaluation tools opens the possibility for participation and sharing of responsibilities for the results achieved and qualifies decision-making.
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2
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LANA CRISTINA EVANGELISTA FERREIRA SA
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Disentangling the effects of irregular parasite shedding and imperfect test sensitivity on the microscopy-based detection of Giardia duodenalis in stool samples
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Advisor : RODRIGO GURGEL GONCALVES
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COMMITTEE MEMBERS :
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CARLA NUNES DE ARAUJO
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FABIANA BRANDAO ALVES SILVA
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RODRIGO GURGEL GONCALVES
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ROSÂNGELA MARIA RODRIGUES
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Data: Feb 16, 2023
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Show Abstract
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The parasitic protozoan Giardia duodenalis (‘Giardia’ hereafter) is a leading global cause of diarrhea. As with many other intestinal pathogens, Giardia diagnosis typically involves detecting parasite presence in stool samples. However, not all stool samples drawn from infected individuals contain parasites (due to irregular parasite shedding), and no test can detect the target parasites in 100% of the samples that indeed contain those parasites (due to imperfect test sensitivity). Disentangling the effects of irregular shedding and imperfect sensitivity on parasite detection would help us better understand both transmission dynamics (which heavily depend on parasite-shedding probabilities) and diagnostic-test performance (of which sensitivity is a critical component). Here, we illustrate an approach to separately estimating, under the assumption of no false-positives, the probabilities of Giardia shedding in the stool of infected hosts (denoted θ) and of Giardia detection in Giardia-positive stool samples (true test sensitivity, denoted p). With this information, we then derive corrected estimates of host-infection frequency (Ψ). We collected 1–3 stool samples, in consecutive weeks, from 276 children (4–73 months) attending 8 kindergartens in 4 urban sectors of the Federal District, Brazil. Samples were processed by the spontaneous-sedimentation method and examined via optical microscopy by two independent observers – an expert parasitologist and a graduate student. Using these replicate test results and multi-level hierarchical models, we estimated the probability of Giardia shedding: θ=0.44. We found no evidence that shedding changed with child gender or age, or between stool sample-collection days; that test sensitivity depended on child age; or that infection frequency changed with child age or varied among urban sectors. The average probability that an expert observer, using a single test, detects Giardia in a stool sample drawn from an infected child was estimated at 0.28. Therefore, reaching upper limit of the probability requires increasing θ, which in turn requires drawing, then pooling, replicate stool samples. Our analyses suggest, in sum, that ~56% of stool samples drawn from infected children did not contain Giardia. As no specific test can (or should) detect parasites in parasite-free samples, θ =0.44 measures the upper limit of the probability of detecting Giardia in a single stool sample drawn from an infected child. The only strategy capable of taking this probability beyond this limit is to draw-and-pool replicate samples; with 4 pooled samples. By allowing estimation (and modeling) of pathogen-shedding probabilities (θ), the approach we illustrate paves the way to studying pathogen transmission cycles and performance of microscopy-based diagnostics used in routine practice in unprecedented detail.
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3
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Joana de Albuquerque Ribeiro
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ECTODEX, an electronic identification key to ectoparasites of public-health interest: development and pilot evaluation
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Advisor : RODRIGO GURGEL GONCALVES
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COMMITTEE MEMBERS :
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CLAUDIO MANUEL RODRIGUES
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JULIANA LOTT DE CARVALHO
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MARINA REGINA FRIZZAS
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RODRIGO GURGEL GONCALVES
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Data: Feb 28, 2023
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Show Abstract
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Although critical for the efficient control-surveillance of several major infectious diseases (including plague, spotted fever, or Lyme disease), identification of ectoparasitic arthropods often relies on outdated, incomplete, and hard-to-access printed keys. Aiming to facilitate ectoparasite identification, we developed an Android/iOS app-based pictorial, polytomous key (“EctoDex”) to 34 species of ticks, lice, fleas, and bedbugs of public-health interest. In a pilot evaluation, we compared EctoDex with a printed dichotomous key (“PKey”) in terms of (i) percentage of correct identifications (“accuracy”) and (ii) time taken to complete an identification task (“time”). Moreover, we tested whether and how performance was affected by user traits (e.g., age, gender, background training, or prior expertise) and ectoparasite species. Each of 33 Brazilian users received up to 30 coded ‘problem specimens’ (21 species) preserved in tubes or on microscope-slides, and was asked to identify each specimen to species using EctoDex and PKey (1356 identification tasks in total). After exploratory analyses, we fitted generalized linear mixed models (GLMMs) accounting for dependencies among repeated observations by the same user; of the same specimen; and from same-genus ectoparasites. Our analyses show that EctoDex overall improved ectoparasite identification across users and species, both in terms of accuracy and time, relative to PKey. Accuracy improved by a larger amount among users without specialized training in ectoparasite taxonomy, with GLMM-predicted values rising from ~57.2% (PKey; CI95% [40.8–72.2]) to ~77.1% (EctoDex; [63.5–86.8]), than among users with such specialized training – whose accuracy rose only slightly, from ~73.1% (PKey; [60.4–82.9]) to ~74.4% (EctoDex; [62.0–83.9]). Identifications by users with high prior expertise were overall more accurate (EctoDex: ~87%; PKey: ~81%) than those by non-expert users (~59% and ~47%, respectively); in contrast, user age, gender, or background general training did not significantly affect accuracy with either key. Accuracy varied widely across ectoparasite species, ranging from 12–18% for the tick, Amblyomma parvum to ~98–99% for the louse, Pediculus humanus. Time GLMMs also showed that EctoDex speeded-up identification tasks particularly for users without specialized training in ectoparasite taxonomy (PKey: ~2.8 min/task, [2.3–4.0]; EctoDex: ~2.0 min/task, [1.4–2.8]); time-saving was modest for users with such training (PKey: ~2.5 min/task, [1.9–3.3]; EctoDex: ~2.1 min/task, [1.6–2.8]). Again, high prior expertise also led to large time-savings (~1.5 min/task, on average, vs. ~3.7 min/task for non-experts), and user age, gender, or background general training did not significantly affect time-to-identification. We also found large among-species variation, with average predicted values ranging from ~3–4 min/task for A. sculptum to ~1 min/task for P. humanus. We conclude that EctoDex holds promise as a means to improve ectoparasite identification in terms of both accuracy and time-savings. Improvements were larger for users lacking formal specialized taxonomic training – whose overall performance, when using EctoDex, became comparable to that of formally trained users. Our pilot study also highlighted, however, the substantial difficulties inherent to identifying some ectoparasites of public-health interest, including several tick species in the genus Amblyomma.
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4
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Ana Luisa Alves Nogueira Barros
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SYNTHESIS, CHARACTERIZATION AND EVALUATION OF THE ANTI-SARS-COV-2 ACTIVITY OF A BIOACTIVE PEPTIDE IDENTIFIED IN THE TRANSCRIPTOME OF FIRE SALAMANDER (SALAMANDRA SALAMANDRA).
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Advisor : JOSE ROBERTO DE SOUZA DE ALMEIDA LEITE
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COMMITTEE MEMBERS :
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ANDREANNE GOMES VASCONCELOS
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JOSE ROBERTO DE SOUZA DE ALMEIDA LEITE
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RÚBEN MIGUEL PEREIRA FERNANDES
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TATIANA KARLA DOS SANTOS BORGES
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Data: Mar 10, 2023
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Show Abstract
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Amphibians of the Urodela order, salamanders and newts, comprise a rich source of molecules with bioactive properties, especially those isolated from the secretion excreted in the skin, with antimicrobial, antioxidant, vasoactive properties, modulating the immune system, among others. In 2020, the COVID19 disease pandemic began, caused by the severe acute respiratory syndrome virus coronavirus 2 (SARS-Cov-2), which resulted in thousands of deaths. This highlighted the importance of studies of new substances to guide the production of therapeutic and prophylactic drugs for infectious diseases. Considering this, this work aimed to carry out a literature review regarding molecules from urodels, with emphasis on their biological activities and to synthesize and evaluate the anti-SARS-Cov-2 activity of a peptide identified in the transcriptome of the fire salamander (Salamander salamander). The literature presents several classes of urodelar molecules, especially peptides and alkaloids. The identified and synthesized peptide, defensin SS-1, belongs to the class of defensins and the in silico 3D molecular docking experiment performed between the enzyme-linker complex with Spike WT RBD/hACE2 and the peptide linker demonstrate its interaction with the binding site active. Although further studies are needed, the preliminary impact of SS1 defensin evaluated in silico in assay illustrated its potential as a promising molecule for drug development in the treatment of COVID19 disease.
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5
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Vanessa Cavalcante de Sena
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Viral Hepatitis C: mortality and multiple-cause-of-death study in the Federal District, Brazil.
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Advisor : MARIA REGINA FERNANDES DE OLIVEIRA
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COMMITTEE MEMBERS :
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MARIA REGINA FERNANDES DE OLIVEIRA
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ELISABETH CARMEN DUARTE
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WILDO NAVEGANTES DE ARAUJO
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GERUSA MARIA FIGUEIREDO
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Data: Jun 5, 2023
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Show Abstract
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Research shows that, despite the adoption of a single death certificate model and an exact definition of the underlying cause, mortality statistics are still not completely accurate. Hepatitis C is an inflammation of the liver and its mortality rate is calculated from the underlying cause. This indicator is used to estimate the risk of dying from this disease and scale its magnitude; however, it does not fully reflect the contribution of hepatitis C to mortality, since this pathology is mentioned in the Death Certificate (DC) as an associated cause in many deaths where death is attributed to other underlying causes. Considering that, in the Federal District (DF), from 2017 to 2021, more than 65.1% of deaths of patients with viral hepatitis were attributed to other basic causes, this study was justified by the need to broaden the look at this topic and identify how patients with hepatitis C are dying. This was a descriptive epidemiological study that aimed to describe the deaths with mention of hepatitis C in the DC, of residents in the DF, which occurred in the period from 2006 to 2020. The official, non-nominal databases of the Information System on Mortality. For data extraction and analysis, TabWin, Microsoft Excel and Stata software were used, as well as population estimates from the Federal District Planning Company. For trend analysis, Prais-Winsten linear regression was performed. Between 2006 and 2020, 487 deaths with mention of hepatitis C were recorded. Of these, 229 (47.0%) had hepatitis C as the underlying cause and 258 (53.0%) had hepatitis C only as an associated cause. In the 229 DC in which hepatitis C is registered as the underlying cause, the most frequent consequential causes were “other and unspecified forms of liver cirrhosis”, “septicemia” and “acute, chronic or unspecified liver failure”. In the 258 deaths that had hepatitis C as an associated cause, the most frequent underlying causes were “liver cell carcinoma or malignant neoplasm of the liver, unspecified”, “HIV disease resulting in other infections” and “alcoholic liver cirrhosis”. Mortality rates for hepatitis C as the underlying cause and those for hepatitis C + carcinoma showed stationary trends for the overall coefficient, for males and for the age groups 50 to 69 years and 70 years or older; and decreasing trends for females and the 30-49 age group. Both in the group that had hepatitis C as the underlying cause and in the group that had it as an associated cause, the highest percentage of people were between 50 and 69 years old, male, white and had incomplete higher education. This study showed that hepatitis C was under-measured as the underlying cause of death and also the need to train professionals who fill out the DC and to improve the rules for selection of the underlying cause and the SCB system.
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6
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Jeanne Fernandes Pereira
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COVID-19 influence on the leprosy treatment adherence in a Brazilian public hospital
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Advisor : INGRID FERREIRA METZGER
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COMMITTEE MEMBERS :
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CIRO MARTINS GOMES
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GUSTAVO LAINE ARAUJO DE OLIVEIRA
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INGRID FERREIRA METZGER
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MICHELINE MARIE MILWARD DE AZEVEDO MEINERS
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Data: Jun 6, 2023
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Show Abstract
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Leprosy is considered a serious public health problem worldwide. It is a disease caused by Mycobacterium leprae with high potential to induce incapacitation. Low treatment adherence is responsible for transmission outbreaks, incomplete cure, therapeutic resistance and increased patient´s irreversible damage. During Covid-19 pandemic, started on March 11 of 2020, according to the World Health Organization, several patients did avoid to seek public health services due to social isolation measures. Thus, the retrospective, observational study aimed to evaluate treatment adherence in patients with leprosy followed at the University Hospital of Brasília-DF before and during the Covid-19 pandemic. The study included 71 patients, older than 18 years old, who started and completed leprosy treatment between January 2018 and December 2021. Sociodemographic and clinical data was collected from patient´s monitoring forms and electronic medical records. Adherence to treatment was measured based on the percentage of drug refilled at the Dermatology outpatient clinic of HUB in first 6 months for PB patients and the first 12 months for MB patients. Adherent patients were considered those who used at least 80% of the total number of pills recommended for leprosy treatment. The study showed that 90.1% of the patients had adherence to the treatment, 53.5% were female, 71,8% were brown and the age mean were 44.5±12.9 years. Comparing adherent and non-adherent patient´s groups regarding sex, age, race, previous treatment, adverse reactions, polypharmacy, single treatment, and leprosy episode, we did not observe any statistical difference. But, comparing these groups regarding the presence of comorbidity, we observed a higher frequency of comorbidity in the non-adherent group (85.7%) than in the adherent group (32.8%), with p value = 0.0105. We also observe that patients that receive the leprosys treatment during the Covid-19 pandemic had higher tendency for non-adherence, in comparison with those treated without the influence of Covid-19. This study showed that patients with comorbidities are more non-adherent, and also shown that pandemic did not have significative influence on patient´s treatment for leprosy, despite the tendency of higher non-adherence in patients treated during the Covid-19 pandemic. Those facts demonstrate that it is necessary implement public policies to help health professionals to maintain the existing care and assume co-responsibility for those patients who tend not to accept the disease and treatment, avoiding the evolution of the disease, as well as its possible complications and streaming.
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7
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RAFAEL DA SILVA FARIA
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Analysis of the spatial distribution of SARS-CoV-2 seroprevalence in a socioeconomically vulnerable population in the Federal District, Brazil
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Advisor : WALTER MASSA RAMALHO
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COMMITTEE MEMBERS :
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ANA IZABEL PASSARELLA TEIXEIRA
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Carlos Frederico Campelo de Albuquerque e Melo
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ELISABETH CARMEN DUARTE
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WALTER MASSA RAMALHO
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Data: Jun 7, 2023
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Show Abstract
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Introduction: The SARS-COV-2 virus spread throughout the Federal District, reaching the SCIA/Estrutural Administrative Region, a socioeconomically vulnerable region. The majority of individuals affected by SARS-CoV-2 are asymptomatic, and due to the lack of apparent symptoms, they do not seek medical assistance. As a result, a considerable amount of asymptomatic individuals are not detected, leading to underreporting. In this context, the use of seroprevalence surveys to detect the presence of antibodies against the virus in the population is extremely relevant, aiming to estimate the number of people who have been infected. In general, the research aims to determine the seroprevalence of SARS-CoV-2 and stratify the risk of infection in the Estrutural population. Methods: A seroepidemiological survey was conducted in Estrutural between May 27th and September 19th, 2021, applying questionnaires and collecting blood samples for serological testing of IgG antibodies for SARS-CoV-2. The sample consisted of 1057 participants for prevalence estimation and statistical analysis, and 1054 participants for spatial analysis. The collection locations were previously randomly selected. At the residence, participant selection was randomly defined using a table of random numbers. The prevalence in the population was estimated, and a binary logistic regression model was applied. The spatial distribution analysis of cases was performed with the creation of a Kernel density map, and the spatial Scan statistic was applied. Results: Of the 1057 participants, 202 had a positive serological result for SARS-CoV- 2. The estimated prevalence was 19.11% (95% CI; 16.85% to 21.59%). When considering a possible influence of the CoronaVac vaccine, the prevalence was estimated at 17.03% (95% CI; 14.83% to 19.46%). In the logistic regression model, a negative association was found between positive cases and having a monthly income of up to one minimum wage (OR = 0.46; 95% CI 0.25 to 0.83), being the only statistically significant category in all models (p = 0.01). The spatial analysis with the Kernel density estimator shows that Chácara Santa Luzia is the region with the highest density of SARS-CoV-2 infection. The Scan spatial statistic showed a cluster in the Santa Luzia region, but it was not statistically significant (p = 0.5). However, the Scan statistic showed a 5.33 higher relative risk within the cluster radius when compared to the exterior. Conclusion: The study shows the existence of a high prevalence of SARS- CoV-2 virus infection in the SCIA/Estrutural Administrative Region. The result is concerning because it is a region of high socioeconomic vulnerability. The protective effect presented by lower income raises the discussion about the relationship between low income and social isolation. The spatial analysis shows a region with a higher density of cases and also a cluster of higher risk of SARS-CoV-2 infection in the Santa Luzia region. This finding goes against our main hypothesis, that the distribution of positive cases of SARS-CoV-2 infection in the Estrutural Administrative Region is not homogeneous and not random.
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8
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Ivea Rayane Mendes Nicacio Viana
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VACCINATION COVERAGE AND FACTORS ASSOCIATED WITH INCOMPLETE VACCINATION SCHEDULE IN CHILDREN FROM SIX MONTHS TO UNDER FIVE YEARS OLD IN BASIC HEALTH UNITS IN THE FEDERAL DISTRICT
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Advisor : HENRY MAIA PEIXOTO
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COMMITTEE MEMBERS :
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HENRY MAIA PEIXOTO
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ISIS POLIANNA SILVA FERREIRA DE CARVALHO
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RODOLFO REGO DEUSDARA RODRIGUES
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RODRIGO LUIZ CARREGARO
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Data: Jun 28, 2023
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Show Abstract
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ABSTRACT: Introduction: The National Immunization Program (PNI) through the vaccines of the basic schedule has been promoting the eradication, elimination, or reduction in terms of incidence, severity, and lethality of various infectious diseases. This fact can be proven with the eradication of smallpox in 1980 and the elimination of polio in the country in 1994. However, in recent years there has been a decline in vaccination coverage (VC), leading Brazil to face significant outbreaks of wild yellow fever and measles. These VC indicators are mostly based on the number of doses applied contained in the information system and do not allow the analysis of factors that lead to non-vaccination, thus, the household vaccination survey is essential for adequate monitoring of vaccination programs, identification of children who are delayed on their vaccination schedule and the factors that lead to this non-vaccination. Objective: The present study estimated vaccination coverage and analyzed the factors associated with incomplete vaccination schedules in children from six months to under five years old in Primary Health Care Units (PHCU) 01 and 04 of Riacho Fundo II in the Federal District. Method: A standardized questionnaire answered by the child's mother or guardian and photographic record of the vaccination card were used. A total of 162 probabilistically selected people were interviewed in the PHCU territories. The study estimated vaccination coverage, the proportion of incomplete vaccination schedules, and used Prevalence Ratios (PR) and their confidence intervals (CI 95%) to estimate the associations between independent variables and the outcome in question (incomplete vaccination schedules), for this purpose, a Poisson regression with robust adjustment was employed. Results: 80% (130/162) of the children evaluated had a complete vaccination schedules. However, none of the vaccines evaluated reached the vaccination coverage recommended by the Ministry of Health, considering the doses administered correctly in terms of age and interval between doses. The results ranged from 46.91% (CI 95%: 39.04%-54.90%) to 77.16% (CI 95%: 69.92%- 83.38%) for the pentavalent and rotavirus vaccines, respectively. Considering only valid doses, that is, doses applied from the recommended minimum age and with an interval equal to or greater than the recommended one, the results were more favorable, ranging from 93.29% (CI 95%: 88.80%- 96.73%) to 99.39% (CI 95% : 96.61%- 99.98%), for the varicella and pneumococcal vaccines, respectively. Factors associated with incomplete vaccination schedules were age under 2 years (adjusted PR: 2.55, CI 95% -1.53-4.24), indication of difficulties arising from the Covid-19 pandemic by those responsible (adjusted PR: 2.71, CI 95% - 1.51-4.86), and a negative response when asked if all vaccines were administered in the same location (adjusted PR: 1.97, CI 95% - 1.13-3.44). Conclusion: The results showed that vaccination coverage did not reach the goals recommended by the Ministry of Health, although it was more favorable when considering only valid doses. In addition, age under 2 years, difficulties arising from the Covid-19 pandemic, and lack of vaccination in the same location were identified as factors significantly associated with incomplete vaccination schedules. These findings highlight the importance of understanding local factors and knowing vaccination coverage to achieve the goals recommended for VC.
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9
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Maria Isabella Claudino Haslett
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Outpatient syndromic surveillance for urban respiratory infectious agents and arboviruses transmitted by Aedes aegypti, in vulnerable population of the Federal District, 2022
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Advisor : WILDO NAVEGANTES DE ARAUJO
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COMMITTEE MEMBERS :
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WILDO NAVEGANTES DE ARAUJO
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MARCOS TAKASHI OBARA
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WALTER MASSA RAMALHO
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Jadher Pércio
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Data: Jul 12, 2023
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Show Abstract
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Introduction: With the Covid-19 pandemic, we realized the need to revisit our traditional surveillance models, shifting away from an epidemiological surveillance conception focused on detection, to a syndromic approach, which enables real-time knowledge, timely response, and systematic monitoring of the population and environment health, and human-environment interaction. The study aimed to describe the epidemiological findings of population-based syndromic surveillance for respiratory infectious agents and urban arboviruses transmitted by Aedes aegypti in primary healthcare, in a socioenvironmental vulnerable area in the Federal District. Methods: We set up a descriptive study with people living at SCIA/Estrutural, with > 1 year old, who went to the health unit for medical assistance between January-December/2022. On free demand, suspected cases were those who reported acute or referred febrile manifestation, with one or more illness-related signs and symptoms. Participants were interviewed in the health unit with a structured online form. Biological samples were collected for diagnosis - nasopharyngeal swabs for respiratory diagnosis (RT-PCR), and blood for arboviruses diagnosis (RT-PCR/serology). All participants signed the consent form. Results: 987 participants were enrolled in the study: 63.0% (622/987) were female; median age was 30 years (IQR: 24-42); 60.9% (601/987) self-declared Hispanic, and 39.8% (393/987) with high school education. From nasopharyngeal samples (n=985), SARS-CoV-2 was detected in 20.4% (201/985); among the negative ones for this analysis (n=784), in 42.6% (334/784) Influenza A serotypes were detected; 26.3% (206/784) had Haemophilus influenzae, and 21.7% (170/784) Human Rhinovirus. Of blood samples (n=878), 9.2% (81/878) had some arbovirus detection: 58.0% (47/81) DENV; 30.9% (25/81) CHIKV, and 2.5% (2/81) ZIKV. Co-detections between arboviruses occurred in 8.6% (7/81) of the cases. Regardless of the etiological agent, the most frequent signs and symptoms for confirmed cases were headache, cough, coryza, sore throat, and myalgia. Overall, 27.4% (215/784) remained undiagnosed. No serious cases or deaths were detected. Conclusions: The syndromic approach and laboratory diagnosis collaborated with surveillance sensitivity and opportunity, at the local level, and offered an accurate diagnosis for the population. Demonstrated that continuous and systematic data monitoring enables more timely interventions, mitigating the impact on the populations and on the health system. We recommend that the syndromic approach in health surveillance become a priority agenda for public health so that it can become a health policy and no longer an individual/specific initiative.
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10
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Vanessa da Silva Eschimith
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EVALUATION OF AN ALKALOID FROM Pilocarpus microphyllus ON THE FUNCTION OF IMMORTALISED MICROGLIA
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Advisor : SELMA APARECIDA SOUZA KUCKELHAUS
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COMMITTEE MEMBERS :
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HELIARA MARIA SPINA CANELA
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LUIZ ANTONIO SOARES ROMEIRO
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SELMA APARECIDA SOUZA KUCKELHAUS
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THAIS TAMARA CASTRO E SOUZA MINUZZI
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Data: Oct 30, 2023
Ata de defesa assinada:
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Show Abstract
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Introduction: The search for new molecules is important to counteract the large number of infectious agents, diseases and conditions through the mechanisms of drug resistance and tolerance. Alkaloids are a broad group of molecules whose biological activity has been increasingly explored due to their ability to interact with cell receptors and proteins. Epiisopilosin (EPIIS) obtained from the species Pilocarpus microphyllus has low cytotoxicity and anti-inflammatory effects. Considering the function of macrophages in the immune system, this study evaluated the effect of different concentrations of EPIIS on the innate function of immortalized macrophages/microglia. Material and Methods: This is an experimental, descriptive and in vitro study carried out with C20 (human microglia) and BV2 (murine microglia) cells to evaluate the effect of different concentrations of EPIIS on cell viability (MTT method and chemiluminescence), cell adherence on coverslips, and by flow cytometry, the production of reactive oxygen (EROS) and nitrogen (ERNS) species, the production of lipid corpuscles (LC) and cytokines; by morphological method, the phagocytic index (PI) and the production of the superoxide radical were assessed (O2º). Results: 1) the different concentrations (0.5 to 128 µg/mL) did not affect the mitochondrial metabolism of C-20 cells when incubated for 24 h (MTT test); 2) chemiluminescence showed that 1 or 4 at 32 µg/mL increased the mitochondrial activity/viability of C-20 cells, but reduced it with 128 µg/mL; 3) incubation of BV-2 cells with 0.5 µg/mL/2h or with 32, 64 or 128 µg/mL for 24 h increased the % of viable cells (MTT test), but the other concentrations did not affect the mitochondrial metabolism of the cells (2 or 24 h); 4) there was a reduction in the % of adhered C-20 cells by incubation for 24 h with 4.0 or 64.0 µg/mL; 5) the highest concentration (64.0 µg/mL) increased the stimulated or basal production of EROS and the basal production of ERNS by C-20 cells; 6) the stimulated production of ERNS (LPS or LPS + TNF) was inhibited by C-20 cells with 64.0 µg/mL; 7) the basal production of CL was higher in C-20 cells with 0.5 µg/mL, but the stimulated one (LPS) was inhibited with 64.0 µg/mL; 8) the lowest concentration (0.5 µg/mL) increased the basal production of IL-17A in C-20 cells, but was inhibited in the presence of LPS at 0.5, 4.0 or 64.0 µg/mL; 9) the three concentrations of EPIIS did not affect the basal production of the cytokines IL-2, IL-6, NTF, INF, IL-4 or IL-10 in C-20 cells; 10) 4 µg/mL/2h increased the IF of BV-2 cells by the highest % of phagocytizing cells (%cels), while 0.5 or 4.0 µg/mL for 24 h reduced the IF by the lowest %cels and the lowest number of yeasts ingested (Mlev). As for the incubation time (2 or 24 hours) with BV-2 cells, the results showed that: 11) there was a reduction in the production of the O2º radical at the three concentrations at 2 h, but not at 24 h; 12) compared to 2 h, there was an increase in Mlev at 64 µg/mL/24 h; 13) the IF was higher at 24 h in the control, than at 2 h, due to the higher %cels and Mlev; 14) the production of the O2º radical was higher at 64 µg/mL/24 h, compared to 2 h. Conclusion: All the functional tests showed that the three concentrations of EPIIS affected the mitochondrial activity of microglia, the expression of adhesion receptors, the production of EROS and ERNS, the production of lipid corpuscles/cytokines and phagocytic capacity, demonstrating the potential of EPIIS to modulate the innate immune response of microglia, thus suggesting the continuation of studies aimed at future biomedical applications in vivo.
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11
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Maria Clara dos Santos Barros Martins
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Epidemiological Analysis of Canine Visceral Leishmaniasis in the Federal District (2005-2022): Investigation of Factors Associated with the Seroprevalence of CVL
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Advisor : CECILIA BEATRIZ FIUZA FAVALI
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COMMITTEE MEMBERS :
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CECILIA BEATRIZ FIUZA FAVALI
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DEBORAH BITTENCOURT MOTHÉ FRAGA
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HENRY MAIA PEIXOTO
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NADJAR NITZ SILVA LOCIKS DE ARAUJO
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Data: Nov 7, 2023
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Show Abstract
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Visceral Leishmaniasis (VL), caused by the species Leishmania infantum, represents a serious threat to both the human and canine populations, as it is considered the most severe and potentially fatal form of leishmaniasis. Dogs are considered domestic reservoirs of the disease, with an increase in human cases typically preceded by an increase in canine cases. Identifying infected animals is a challenge, as Canine Visceral Leishmaniasis (CVL) presents complex and often nonspecific clinical signs, with a significant proportion of asymptomatic dogs. Using secondary data from the Directorate of Environmental Surveillance of the Federal District (DIVAL-DF) and epidemiological reports, this study investigates the evolution and epidemiological situation of the canine population in the Federal District (DF), identifying individual risk factors associated with a positive clinical outcome for CVL. From 2005 to 2022, a seropositivity rate of 15.8% was found through the serological testing of 59,762 dogs. Characteristics associated with a higher seropositivity for CVL included the presence of apparent clinical signs (OR = 1.88; 95% CI: 1.73-2.05), age over six years (OR = 1.46; 95% CI: 1.32-1.62), short coat (OR = 1.32; 95% CI: 1.17-1.48), and male gender (OR = 1.10; 95% CI: 1.02-1.18). The results reaffirm the endemicity of leishmaniasis in the DF and a significantly high canine seroprevalence, with the identification of risk groups and areas showing a stronger association with a positive diagnosis for the disease. Therefore, the adoption of individual prevention and control measures, such as the use of insecticide-impregnated collars, vaccination, and dog treatment, may be an attempt to reduce the incidence of CVL.
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12
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JANET SALLIS NIMOH MENSAH
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SEROEPIDEMIOLOGICAL SURVEY FOR THE DETECTION OF MEASLES VIRUS ANTIBODIES IN THE ADMINISTRATIVE REGION OF SCIA-ESTRUTURAL, FEDERAL DISTRICT, JUNE-NOVEMBER 2021
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Advisor : WILDO NAVEGANTES DE ARAUJO
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COMMITTEE MEMBERS :
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MAURO NISKIER SANCHEZ
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WILDO NAVEGANTES DE ARAUJO
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VANESSA RESENDE NOGUEIRA CRUVINEL
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WANDERSON KLEBER DE OLIVEIRA
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Data: Dec 7, 2023
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Show Abstract
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Background & objectives: Measles is a highly contagious infectious disease with possible lethal consequences; though, it is preventable through vaccination. Vaccination/immunization has proven to be the most efficient measure in preventing and reducing incident cases and deaths caused by the measles virus amongst the population. This study aims at analyzing the seroprevalence of measles within the SCIA- Estrutural-DF community, and to identify the factors associated with the presence of the virus. Methods: Sero epidemiological survey was conducted with a sample size of 890 individuals. After seeking participants' consent, interviews were conducted, and blood samples were collected for serological testing, employing the ELISA technique, to detect IgG antibodies. The data collected were subsequently processed using the software application Jamovi version 2.3.21 and subjected to analysis through descriptive and Poisson statistical methods. Results: The estimated overall seroprevalence was 633/890 [71.1%; 95% CI: 68.0%-74.0%]. The mean age of the general population was 38.4 years (95% CI 35y-42y), standard deviation 14.5, median age 38 years. Regarding gender, 581/890 (65.3%; 95% CI 62.2-68.4) were female; of these, 417/581 (71.7%; 95% CI: 70.0-73.0) were seropositive. There was a high (83% CI 95%; 80.3-85.7) prevalence of seropositives in the 41-60, and >60 age groups (92.6% CI 95% 90.9%-94.3%)], Statistically analyzed after adjustments, the 0-19 age group had an 18% higher prevalence of antibodies [RP 1.18 CI 1.04-1.33 p= 0.009) when compared to the 20-40 age group, as well as 61% (PR 1.61 95% CI 1.19-2.19, p<0.002)) higher prevalence for the over-60years age group when compared to the 0-19years age group. Conclusion: Actions are required to enhance vaccination coverage among the population of the SCIA-Estrutural AR community and to homogenize the distribution of seropositive individuals across different age groups through proactive immunization. Subsequent studies will be necessary to evaluate the levels of measles antibodies in the studied population, as well as further studies needed to confer the level of antibody titers among the population.
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Thesis |
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1
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Kauara Brito Campos
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SUSCEPTIBILITY OF Ae. aegypti TO THE INSECTICIDES PYRIPROXYFEN AND MALATHION AND THE CAPACITY OF ZIKA VIRUS INFECTION IN POPULATIONS RESISTANT TO PYRIPROXYFEN
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Advisor : MARCOS TAKASHI OBARA
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COMMITTEE MEMBERS :
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MARCOS TAKASHI OBARA
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RODRIGO GURGEL GONCALVES
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DINAIR COUTO LIMA
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Grasielle Caldas DÁvila Pessoa
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JULIANA TELLES DE DEUS
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Data: Jun 15, 2023
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Show Abstract
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Introduction: Aedes aegypti chemical control in Brazil remains the main tool for preventing arboviral outbreaks. Monitoring the vector's susceptibility to insecticides is essential for replacing substances in case of confirmed resistance. Still, the relationship between resistant mosquitoes and the ability to infect arboviruses is little explored and unclear, especially with the Zika virus (ZKV). Objectives: To analyze the susceptibility of Ae. aegypti populations to the insecticides pyriproxyfen (PPF) and malathion between 2017 and 2018 in Brazil, as well as to reassess the evolution of PPF resistance after two years of exposure to bimonthly applications of the larvicide; and to investigate the relationship betweenresistant mosquitoes to PPF and its ability to be infected by ZIKV. Methods: Ae. aegypti eggs were collected in 132 cities using oviposition traps. Colonies were subjected to susceptibility tests with larvae exposed to the Diagnostic Dose (DD) of PPF (0.3 µg/L) and adults with the DD of malathion obtained in our laboratory (20 µg), in addition to the DD indicated by the World Health Organization (WHO) (50 µg) in bottle assay. Subsequently, DoseResponse (DR) bioassays with PPF were performed in populations with EI < 98% to estimate the RR. In 2020, eggs were collected in cities where we previously recorded PPF resistance for new DR bioassays. Mosquitoes from populations with different resistance levels to PPF and an insecticide-susceptible strain (Rockefeller) were experimentally orally infected with ZIKV to determine their relative vector competence. Results: Changes in susceptibility to PPF were recorded in 6 (4.5%) populations, in Bahia and Ceará states, with a Resistance Ratio (RR) from 1.51 to 3.58. For malathion, 73 (55.3%) of the populations distributed in the country were resistant when exposed to local DD (20 µg/bottle). On the other hand, no population was resistant, and only 10 (7.6%) populations showed reduced susceptibility (mortality rate 90 to 98%) when the WHO DD (50 µg/bottle) was used. In 2020, mosquitoes from Icó, Serrinha, and Brumado showed low levels of PPF resistance (RR50= 2.33, 4.52, and 4.83, respectively); moderate levels were detected in populations from Juazeiro do Norte (RR50=5.83) and Itabuna (RR50=7.88), and high level in Quixadá (RR50=11). Although all populations were competent to become infected with ZIKV, those with moderate to high levels of insecticide resistance (IR) exhibited similar or lower susceptibility to ZIKV infection compared to populations with low IR or the strain susceptible. Conclusions: Resistance to PPF was registered in Ae. aegypti populations from northeastern Brazil; as well as the local DD for malathion (20 µg/bottle) was more sensitive than the WHO one (50 µg/bottle) for early detection of decreased susceptibility; the evolution of this resistance can compromise efforts to control it, and continuous monitoring is essential for effective insecticide management. The use of PPF to control Ae. aegypti may be associated with the indirect benefit of reduced susceptibility to ZIKV infection without changes in disseminated infection and transmission of this arbovirus among PPF-resistant phenotypes.
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2
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Patrícia Matias Pinheiro
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PRE-EXPOSURE PROPHYLAXIS (PREP): FROM THE TURNING POINT IN HIV PREVENTION TO THE CHALLENGE OF ADHERENCE
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Advisor : WILDO NAVEGANTES DE ARAUJO
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COMMITTEE MEMBERS :
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ELZA FERREIRA NORONHA
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HERMANO ALEXADNRE LIMA ROCHA
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Jadher Pércio
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RODOLFO REGO DEUSDARA RODRIGUES
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WILDO NAVEGANTES DE ARAUJO
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Data: Jul 20, 2023
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Show Abstract
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Introduction: PrEP (Post Exposure Prophylaxis) consists of the use of antiretrovirals used by patients who are at increased risk of HIV infection. It is an effective epidemic control strategy, however if fully adopted. Objective: To describe the profile of patients using PrEP and the factors associated with dropout and discontinuation rates in Brazil from 2018 to 2020. Materials and Methods: Four studies were developed. The first, cross-sectional, evaluated the difference in profile between users of a PrEP, service and another for STI screening. The second, case-control that investigated the factors associated with dropout rates in the first 30 days of therapy. The third, case-control, showed the factors associated with discontinuing PrEP for reasons such as: poor adherence to the medication, adverse events, acute HIV infection. The last, a cohort that evaluated the risk behavior of patients before and after starting PrEP. Data came from primary databases, collected from 2020 to 2021 at a PrEP service at a tertiary hospital and at a public Testing and Counseling Center in the Federal District, Brazil. Secondary data were extracted from SICLOM, totaling 34,000 people and containing data from users of the national database from 2018 to 2020. Results: The study showed that PrEP users are homosexual or MSM (89%), with a mean age age of 33 ± 9 years; 68% with more than 12 years of study. Before starting PrEP, 10.4% did not use condoms and after that it increased to 24.7%, showing some risk compensation. Dropout rates in the first 30 days were 22.25% and the main factors were: sexual orientation (ORa: 0.81; 95%CI:0.71-0.91; p<0.01), race (ORa: 1.15; 95%CI: 1.08-1.22 p<0.001), education (ORa:1.54; 95%CI: 1.35-1.76 p<0.001), reason for seeking PrEP (ORa:1.21; 95%CI:1.14-1.30, p<0.001) , PEP use (ORa:0.94, 95%CI: 0.91-0.98, p<0.001), frequency of condom use more than half of the time (ORa: 0.8595%CI: 0.78-0.93, p<0.001), sex in exchange of money(ORa: 0.82CI95%: 0.73-0.91, p<0.001), use of substances, such as: poppers (ORa: 0.65, CI95%: 0.54-0.78, p<0.001), cocaine (ORa: 1.22, CI95%: 1.08-1.37p=0.002), clubs drugs (ORa: 0.79, CI95%:0.70-0.89, p<0.001) and erection stimulants (ORa: 0.64, CI95%: 0.56-0.72, p<0.001) and symptoms of acute viral infection (ORa: 0.80, 95%CI: 0.71-0.89, p<0.001) . The interruption had the following profile: 83% were men, aged between 30-39 years (34%), motivated by: 23.3% due to changes in tests, 9.0% adverse events, 4.3% due to a positive HIV test, 3.4% due to low medication adherence and 59.8% due to their own decision. Conclusion: The data points to inequality in the access of the most vulnerable populations regarding the risk of HIV infection, requiring policies that make this strategy more inclusive. Even after starting PrEP, patients are still exposed to risks, neglecting effective non-pharmacological preventive measures, especially for other types of STIs. In addition, it was found that the abandonment and interruption of patients have generated challenges in adherence, which can directly affect the good efficacy of the therapy.
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3
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Elane Priscila Maciel
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Inhibitory pathways in human immune response to Leishmania spp
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Advisor : CECILIA BEATRIZ FIUZA FAVALI
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COMMITTEE MEMBERS :
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CECILIA BEATRIZ FIUZA FAVALI
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VICENTE DE PAULO MARTINS
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CLARISSA ROMERO TEIXEIRA
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NATALIA MACHADO TAVARES
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SHÉLIDA VASCONCELOS BRAZ
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Data: Sep 22, 2023
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Show Abstract
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INTRODUCTION Leishmania braziliensis causes a proinflammatory disease, with localized lesions and a possible mucosal commitment. On the other hand, Leishmania infantum is involved in the visceral form, with a specific cellular response anergy. Previous data from our group showed that DC-SIGN expression in moDCs (monocytes derived Dendritic Cells) was decreased after L. braziliensis and L. infantum infection, probably compromising DC function and T cell activation, as a parasite scape mechanism. Besides that, parasites can induce inhibitory molecules that also could be involved in T cell anergy. METHODS This research focused the PD1-PDL1 pathway in human moDCs infected with L. braziliensis or L. infantum, studying cell surface molecules expression as well as antibodies to block PD1-PDL1 pathway. This study was approved by the faculty ethics commission (CEP/FM/UnB - CAAE 33062720.6.0000.5558). RESULTS Infection rate measured with optical microscopy was 76% (±8.83) for L. infantum, while for L. braziliensis it was 50% (±10.97). When determined by flow cytometry, infection rate was 69.05% (±4.56) for L. infantum and 35.25% (±5.56) for L. braziliensis. Was observed a down modulation of DC-SIGN on DCs bystanders (non-infected cells from the same well where Leishmania was added) for L. infantum (64,95% ±9,36) and L. braziliensis (72,4% ±1,71), compared to control DCs (84,70% ±5,07). We also observed an increase on PDL1 in DCs infected with L. braziliensis (99,55% ±19,06) or bystanders (86,85% ±22,24) as well as for DC infected with L. infantum (99,6% ±0,41) or bystander DCs (86,40% ±7,96). By blocking cell co-culture with anti-PDL1, IFN-g production from CD4 cells, raised from 1,94 (±0,91) in L. braziliensis infected DCs to 8,16% (±4,33) when anti-PD-1 was used. The same effect was observed for L. infantum with an increase from 1,79 % (±1,18) to 5,38 (±3,69) when PD1-PDL1 pathway was blocked. For CD8 T cells IFN-g raised from 7,38 (±2,34) in L. braziliensis infection to 21,40 (±7,47) by blocking PD1-PDL1. The same effect was also observed for L. infantum infection, with 5,97 (±1,66) CD8+IFN+ cells and upregulating to 14 (±4,53) by blocking PD1-PDL1. CONCLUSIONS L. braziliensis and L. infantum infection, or their soluble products, increased the expression of PD1 on moDCs, probably impairing T cell IFN-g production that could control parasites spread.
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4
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KLAUSS KLEYDMANN SABINO GARCIA
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Brazil's Progress towards Malaria Elimination: Time Series Analysis of Malaria Cases and Case-Control Study of Factors Associated with Malaria Mortality in Brazil from 2011 to 2022
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Advisor : WALTER MASSA RAMALHO
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COMMITTEE MEMBERS :
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ELISABETH CARMEN DUARTE
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GABRIEL ZORELLO LAPORTA
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MARCUS VINICIUS GUIMARAES DE LACERDA
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SHEILA RODRIGUES RODOVALHO
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WALTER MASSA RAMALHO
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Data: Nov 6, 2023
Ata de defesa assinada:
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Show Abstract
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INTRODUCTION: The World Health Organization estimates that in 2021, approximately 247 million people worldwide were afflicted by malaria, resulting in over 619,000 deaths. In Brazil, malaria is a serious public health issue, particularly in the Amazon region (AMZ), which accounts for 99% of the country's cases. The extra-Amazon region of Brazil registers a higher incidence of imported malaria cases compared to autochthonous cases. Therefore, one of the strategies of the National Malaria Control and Prevention Program is to eliminate the disease by 2035. To reach that the program focus on control strategies in the AMZ region and the prevention of outbreaks in the extra-Amazon region. In 2021, Brazil reported more than 137,000 autochthonous cases of malaria and 61 deaths. Despite the magnitude of malaria in Brazil, uncertainties still exist regarding the factors related to deaths in the country. OBJECTIVES: This thesis aims to describe and analyze the epidemiological scenario of malaria in Brazil from 2011 to 2022 to understand the current situation and anticipate case occurrences in the coming years. Additionally, it seeks to identify factors associated with malaria deaths in Brazil in order to prevent and eliminate such occurrences. METHODS: This thesis comprises four studies analyzing malaria case and death data from 2011 to 2022. Two of these studies have a cross-sectional design, describing and characterizing the epidemiological profiles and scenarios of the AMZ and non- AMZ regions of Brazil, including the development of predictive models (forecasting). The third study is of cross-sectional and methodological nature, reports data record linkage processes that can contribute to improving the quality of malaria death information and enhance death investigation activities. The fourth study is a case-control study, describing the epidemiological profile of malaria deaths among Brazilian residents and investigating factors associated with these deaths. Open data were used for the first two studies, while nominal data were used for the latter two. The research was approved by the Research Ethics Committee of the School of Medicine at the University of Brasília. RESULTS: In the extra-AMZ region, a predominance of imported cases from other countries and the Brazilian AMZ region was identified, mainly related to individuals' occupational activities. In the AMZ region, locally transmitted cases predominate, and the prospective scenario suggests the possibility of malaria elimination in Brazil by 2035. However, this requires overcoming challenges, especially in the states of Amazonas and Roraima, as well as in mining areas and among indigenous populations. Deaths in the country have been increasing since 2019, with higher lethality in the extra-AMZ region, mainly due to cases imported from other countries and high parasitemia infections caused by species such as P. falciparum, P. ovale, and P. malariae. In the AMZ region, deaths are predominantly due to P. vivax infections, with risk factors associated with delays in detection/diagnosis, infections in indigenous areas, infections in children under one year old and adults over 40 years old, high parasitemia, and passive case detection. CONCLUSIONS: This thesis provided a comprehensive understanding of the malaria scenario and epidemiological profile in Brazil, highlighting temporal variations over the years and future case occurrence trends. Furthermore, record linkage techniques allowed investigation of related and associated causes of malaria deaths, offering insights into how this knowledge and these techniques can strengthen public health policies and assist Brazil in its goal to eliminate malaria by 2035.
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