Doutorado em Doenças Infecciosas
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- ItemCaracterização da atividade antimicrobiana dos complexos metálicos Cu-fendiona e Ag-fendiona em cepas clínicas de Acinetobacter baumannii resistentes a carbapenêmicos e com diferentes perfis de virulência(Universidade Federal do Espírito Santo, 2024-11-07) Peregrino, Ingrid Vianez; Santos, André Luís Souza dos; https://orcid.org/0000-0003-0821-8592; http://lattes.cnpq.br/1705068704334079; Nunes, Ana Paula Ferreira; https://orcid.org/0000-0001-7919-2938; http://lattes.cnpq.br/7851528667690358; https://orcid.org/0000-0001-8716-796X; http://lattes.cnpq.br/7607579386275396; Galdino, Anna Clara Milesi; https://orcid.org/0000-0003-1601-8478; http://lattes.cnpq.br/7652165054195655; Sá, Marta Helena Branquinha de; https://orcid.org/0000-0002-9752-8148; http://lattes.cnpq.br/; Palaci, Moisés; https://orcid.org/0000-0003-2013-6071; http://lattes.cnpq.br/2158584413298259; Silva, Quézia Moura da; https://orcid.org/0000-0002-3758-4148; http://lattes.cnpq.br/1778832016290387Continuous efforts are essential for developing new anti-infective agents in response to the increasing threat of antimicrobial resistance. Exploring the pharmacodynamic (PD) properties and activity profiles of antimicrobial candidates enables rational optimization of these compounds' development, maximizing their therapeutic potential. Our research group has been investigating the therapeutic potential of metal-based complexes derived from 1,10-phenanthroline-5,6-dione (phendione) against critical pathogens. Previous studies have demonstrated the efficacy of Ag-phendione and Cu phendione against carbapenem-resistant (CRAb) and multidrug-resistant Acinetobacter baumannii strains, both in planktonic cells and biofilms. In this study, we characterized the antimicrobial activity of Cu-phendione and Ag-phendione and determined their PD parameters against six clinical CRAb strains and the ATCC 19606. We also investigated the antivirulence potential of these compounds by identifying virulence attributes and pathogenic mechanisms in 26 clinical CRAb strains. Exposure response assays revealed strong bactericidal effects at low concentrations, with predominantly time-dependent activity and peak efficacy between 6 and 12 hours. Fractionated dosing strategies showed sustained antimicrobial efficacy, with two 0.5×MIC doses administered 6 hours apart resulting in complete eradication of all strains within 24 hours. Substantial inoculum variations did not significantly alter MIC values, confirming consistent bactericidal activity across different bacterial densities. At 3.12 µg/mL, both compounds were able to eradicate over 97% of the tested inocula. Additionally, both exhibited short post-antibiotic effects (PAE), with Ag-phendione displaying slower growth recovery than Cu-phendione, with average PAE durations of 1.857 h and 0.714 h, respectively. The modified disk-diffusion (“TDtest”) showed no evidence of tolerance or heteroresistance. The investigation of virulence-associated features revealed notable heterogeneity among the studied strains, with variations in levels of mucoviscosity, motility, biofilm formation, and autoaggregation capacity. The analysis of cell surface properties indicated a negative correlation between mucoidy and hydrophobicity levels, while all isolates exhibited an electronegative surface charge. However, no direct correlation was observed between these surface characteristics and biofilm formation capacity. In the Galleria mellonella infection model, larval mortality rates suggested diversity in pathogenic strategies among strains, though no direct correlation was found between specific virulence attributes and overall pathogenicity. While previous studies have demonstrated the antibiofilm activity of these compounds, in the present study, the high heterogeneity of the sample group prevented the evaluation of the complexes' impact on specific virulence attributes. Thus, our conclusions focus on the broad therapeutic potential of Cu phendione and Ag-phendione as promising alternatives for treating CRAb infections, highlighting their antimicrobial properties and favorable PD profiles across diverse resistance and virulence patterns in A. baumannii
- ItemAspectos ecoepidemiológicos e avaliação das ações de vigilância da Doença de Chagas no Espírito Santo(Universidade Federal do Espírito Santo, 2025-05-21) Soares, Stefanie Barbosa Potkul; Leite, Gustavo Rocha ; https://orcid.org/0000-0003-4320-3804; http://lattes.cnpq.br/2276153460276432; Fux, Blima ; https://orcid.org/0000-0002-5038-3551; http://lattes.cnpq.br/5225003149904835; https://orcid.org/0009-0006-1195-4872; http://lattes.cnpq.br/8593162858760954; Vianna, Elisa Neves ; https://orcid.org/0000-0003-2793-5298; http://lattes.cnpq.br/7881831478280535; Ferreira, Cleber Galvão ; https://orcid.org/0000-0003-4027-9205; http://lattes.cnpq.br/5125939848611273; Gomes, Daniel Claúdio de Oliveira ; https://orcid.org/0000-0002-0663-0981; http://lattes.cnpq.br/3965075540969796; Delatorre, Edson Oliveira ; https://orcid.org/0000-0002-5746-0820; http://lattes.cnpq.br/9814839314541002Chagas disease, a chronic and potentially fatal infection caused by the protozoan Trypanosoma cruzi. This study aims to identify ecological and epidemiological factors associated with the distribution of triatomines in the state of Espírito Santo (ES), with a view to improving entomological and epidemiological surveillance. To assess ecological aspects, ecological niche modeling was carried out for triatomine species in ES, recorded between 2004 and 2022. In addition, a risk map for vector transmission in the state was produced. To analyze the epidemiological situation of the state, a descriptive analysis of confirmed cases of Chagas disease was carried out. The data were collected through SINAN (Notifiable Diseases Information System) and SESA (State Health Department of Espirito Santo) between 2001 and 2023. An analysis of Chagas disease surveillance actions was also carried out by applying a questionnaire to managers, disease control agents, and community health agents in some municipalities in the state. Regarding modeling, the maps identified high suitability for most species in the Metropolitan and Southern regions of ES. The risk assessment highlighted significant risk areas corresponding to the locations of these cases, indicating that most regions of ES present a higher risk of the presence of P. megistus and Triatoma vitticeps. 65 cases of Chagas disease were recorded in Espírito Santo between 2001 and 2023. Of the total number of cases, 36.9% were autochthonous, 29.2% were imported, and 33.3% were considered undetermined as to the site of infection. Regarding the results of the questionnaires, it was observed that most health professionals have little knowledge about Chagas disease and did not carry out surveillance actions related to Chagas disease. Most managers stated that there was no work plan aimed at implementing surveillance actions against Chagas disease. These findings provide crucial information to improve regional epidemiological and entomological surveillance and inform targeted vector control strategies
- ItemAnálise da retenção à terapia antirretroviral de pessoas vivendo com HIV e fatores associados no Brasil de 2014 a 2022(Universidade Federal do Espírito Santo, 2025-03-26) Freitas, Marcelo Araújo de; Pascom, Ana Roberta Pati ; https://orcid.org/0000-0002-2646-3383; http://lattes.cnpq.br/1066727701162204; Miranda, Angelica Espinosa Barbosa; https://orcid.org/0000-0002-5556-8379; http://lattes.cnpq.br/5842271060162462; https://orcid.org/0000-0002-0763-233X; http://lattes.cnpq.br/9275784580459018; Mesquita, Fábio Caldas de; https://orcid.org/0000-0002-8297-0224; http://lattes.cnpq.br/5238492147032062; Oliveira, Maria Cristina Pimenta de ; https://orcid.org/0000-0002-4205-9786; http://lattes.cnpq.br/4908168036177095; Teixeira, Carlos Graeff ; https://orcid.org/0000-0003-2725-0061; http://lattes.cnpq.br/0464152494769261; Cerutti Junior, Crispim ; https://orcid.org/0000-0002-9485-4191; http://lattes.cnpq.br/4257067087979999INTRODUCTION: Retention in antiretroviral therapy (ART) is essential for controlling HIV/AIDS and reducing mortality rates worldwide. In Brazil, although ART is widely accessible, challenges remain in maintaining individuals in treatment over time. This study aimed to analyze trends in ART retention from 2014 to 2022 in the country. METHODS: This population-based study used national antiretroviral dispensing databases from the Ministry of Health to assess retention at 6, 12, 24, 36, 48, and 60 months after treatment initiation. The analysis included individuals aged 15 years or older, defining retention as a delay in medication dispensing of no more than 28 days. Additionally, a multivariate analysis was conducted for 60-month retention in the year 2022. RESULTS: The study observed over 3.4 million ART dispensations, revealing that retention steadily declined over time, with the lowest proportions observed at 60 months (71% in 2022). Men had consistently higher retention compared to women (79% vs 73% in 2022). Lower retention was found among younger age groups (74% in 2022), indigenous populations (67% in 2022), individuals with lower education levels (72% in 2022), and those residing in northern (74% in 2022) regions of Brazil. The multivariate analysis of 60-month retention in 2022 found a higher likelihood of retention among individuals without tuberculosis coinfection (OR: 1,26; IC95% 1,17 – 1,36; p=0,000). CONCLUSIONS: The study highlights significant challenges in retention, especially after prolonged ART use, with notable disparities across demographic and regional groups. The findings suggest the need for targeted interventions to improve ART retention, particularly among vulnerable populations, and may support public health policies to strengthen continuous HIV care in Brazil
- ItemRelação entre doença periodontal e doenças crônicas não transmissíveis em usuários do sistema público de saúde - Vila Velha - ES(Universidade Federal do Espírito Santo, 2024-10-08) Mendonça, Gustavo Vital de; Feitosa, Alfredo Carlos Rodrigues ; https://orcid.org/0000-0003-4090-4760; http://lattes.cnpq.br/2076852367700539; Cerutti Junior, Crispim ; https://orcid.org/0000-0002-9485-4191; http://lattes.cnpq.br/4257067087979999; https://orcid.org/0000-0002-4314-9708; http://lattes.cnpq.br/1083615409753183; Pinel, Roberta Gracelli Batitucci ; https://orcid.org/; http://lattes.cnpq.br/2362742785781750; Szpilman, Ana Rosa Murad ; https://orcid.org/0000-0003-1399-3753; http://lattes.cnpq.br/0758783435748999; Pandolfi, Margareth ; https://orcid.org/0000-0001-8921-9356; http://lattes.cnpq.br/6133806025978916; Delatorre, Edson Oliveira ; https://orcid.org/0000-0002-5746-0820; http://lattes.cnpq.br/9814839314541002Periodontal disease (PD) encompasses gingivitis and periodontitis. Gingivitis or inflammation of the gums, which leads to bleeding gums, is considered an early form of periodontal disease. Periodontitis develops over time, with accumulation of dental plaque, bacterial dysbiosis, formation of periodontal pockets, gingival recession, tissue destruction and alveolar bone loss, which can lead to tooth loss. In the late 1980s, dental journals published several observational studies that identified systemic diseases in patients with PD. In the 1990s, the term “periodontal medicine” was introduced. In the early 21st century, dentists began to warn their patients about the potential relationship between PD and a number of systemic diseases. Therefore, we carried out this study with the objectives of describing the relationship between the occurrence of periodontal disease and the prevalence of chronic non-communicable diseases, as much as the influence of the severity of periodontal disease on the prevalence of such chronic conditions. Another objective was to demonstrate the relevance of multidisciplinary care in the public health service. The study population consisted of patients using the public health service in the city of Vila Velha, Espírito Santo. The Jardim Colorado, Divino Espírito Santo and Ataíde health units were used for the study. The CPI (Community Periodontal Index) method was selected, which is recommended by the WHO and the Ministry of Health. The number of lost dental elements was also evaluated. The systemic health assessment was carried out through careful anamnesis, with measurement of blood pressure and blood glucose, and with data self-reported by the volunteers, as well as through the analysis of the citizen's electronic medical record. The association between periodontal disease and the occurrence of chronic non-communicable diseases was verified by simple logistic regression adjusted for confounding factors (age, smoking and excess weight), using comorbidity outcomes (systemic arterial hypertension, diabetes mellitus, ischemic events, arthritis, neurological disorders and cancer) and the independent variables total periodontal index and number of missing teeth. The study population consisted of 334 volunteers. It was possible to find a significant association between the total periodontal index and systemic arterial hypertension and diabetes in patients aged 45 years or over. Also, there was a significant association between the total periodontal index and systemic arterial hypertension, diabetes mellitus and cancer in female individuals, with the participant whose total CPI was 9 to 13 being 2.8 times more likely to have systemic arterial hypertension when compared to the participant with values from 1 to 2. Our findings allow us to conclude that periodontal disease has a positive and statistically significant association with arterial hypertension and diabetes mellitus in the population over 45 years of age, regardless of confounding factors (smoking and excess weight). Severe periodontitis is also a risk factor for cancer in women, and tooth loss is also a risk factor for hypertension and diabetes in women
- ItemTransmissão vertical da infecção pelo HIV e da sífilis na faixa de fronteira terrestre do Brasil de 2010 a 2020(Universidade Federal do Espírito Santo, 2024-01-29) Lannoy, Leonor Henriette de; Co-orientador1; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador2; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador3; https://orcid.org/; http://lattes.cnpq.br/; Co-orientador4; ID do co-orientador4; Lattes do co-orientador4; Miranda, Angelica Espinosa Barbosa ; https://orcid.org/0000-0002-5556-8379; http://lattes.cnpq.br/5842271060162462; Orientador2; https://orcid.org/; http://lattes.cnpq.br/; https://orcid.org/0000-0002-9520-8538; http://lattes.cnpq.br/0999758340503440; Díaz Bermúdez, Ximena Pamela Claudia ; https://orcid.org/0000-0002-3771-7684; http://lattes.cnpq.br/1598351909460233; Brito, Ana Maria de ; https://orcid.org/; http://lattes.cnpq.br/0105337613337822; Teixeira, Carlos Graeff; https://orcid.org/0000-0003-2725-0061; http://lattes.cnpq.br/0464152494769261; Cerutti Junior, Crispim ; https://orcid.org/0000-0002-9485-4191; http://lattes.cnpq.br/4257067087979999; 5º membro da banca; https://orcid.org/; http://lattes.cnpq.br/; 6º membro da banca; https://orcid.org/; http://lattes.cnpq.br/; 7º membro da banca; https://orcid.org/; http://lattes.cnpq.br/Introduction: Mother-to-child (MTCT) of HIV and syphilis (congenital syphilis) are diseases that persist as public health issues in several parts of the world, and have been scarcely studied at the Brazilian land border strip (LBS). Measures to prevent MTCT of HIV and syphilis are widely known and Brazil has the necessary resources and technologies available. The Brazilian LBS is the 3rd largest land border in the world and, for the purposes of planning and promoting regional development, the National Regional Development Policy (PNDR) established the division of the region into three major arcs: North, Central and South. In turn, borders are unique spaces with potential and challenges that require differentiated programmatic public policies that take into account the specificity of each territory. Understanding the epidemiological situation of the problem in the region aims to contribute to the implementation of public policies and support the strategy of eliminating MTCT of HIV and congenital syphilis. Objectives: Understand MTCT of HIV and syphilis and analyze the provision of health services at the Brazilian LBS from 2010 to 2020. Methods: A quantitative, ecological, and cross-sectional evaluation study was conducted using secondary data from cases of HIV/AIDS, HIV in pregnant women, acquired syphilis (AS), syphilis in pregnant women (PS), and congenital syphilis (CS) registered in the Notifiable Diseases Information System (SINAN) between 2010 and 2020 and living in the Brazilian border municipalities. Information from the Live Birth Information System (SINASC), the Primary Care Health Information System (SISAB), the e-Gestor and the Medicines Logistic Control System (SICLOM Managerial) were also used. The variables studied included sociodemographic characteristics, prenatal and delivery data, as well as the availability of services and procedures. Detection rates of AS, PS, AIDS, HIV infection in children under 5 years old, HIV in pregnant women, and the incidence of CS were calculated. The MTCT rate of HIV was estimated based on the number of children infected with HIV per year of birth divided by the number of HIV-infected pregnant women reported by year of delivery. Trends in detection and incidence rates were calculated for the analyzed period. Thematic maps were constructed for spatial distribution analysis of detection rates and incidences using Quantum GIS (QGIS) version 2.18.6, and spatial analysis was evaluated local autocorrelation (local index of spatial association—LISA) by means of Local Moran’s I index, calculated using R software version x64 3.4.0. Results: In the LBS, among pregnant women diagnosed with syphilis, 23.7% were 15 to 19 years old, 34.2% were illiterate or had 14 only primary education, 7% were black, and 47% were of mixed race. Among pregnant women with HIV infection, 15.6% were 15 to 19 years old, 34.0% were illiterate or attended only primary education, 10.1% were black, and 42.1% were of mixed race. It was verified that in 2019 and 2020 approximately 90% of pregnant women in the LBS had four or more prenatal consultations. However, in the Northern arc, this proportion was only 82% in 2019 and 79% in 2020. Information on rapid testing (RT) for syphilis in the SISAB was available on 84% of the municipalities while RT performance for HIV was available on 92% of them. Sixty-eight percent of the municipalities recorded the administration of penicillin for syphilis treatment and 17% of them had Medication Dispensing Units. The time series analysis in the LBS showed a 48% average annual increase in PS case detection rates from 2010 to 2020, being 59.6% in the Northern arc, 28.8% in the Central arc, and 67.2% in the Southern arc. Regarding CS, there was an average increase of 38.4% in the LBS, being 18.3% in the Northern arc, and 65.7% in the Southern arc. The Central Arc showed no statistically significant upward trend in the incidence of CS. The annual variation rate in the detection of pregnant women with HIV infection in the LBS was 9.1%, with an increase of 19.6% in the Northern Arc, 11.4% in the Central Arc and 6.1% in the Southern Arc. On the other hand, the AIDS trend in children under 5 years old showed a reduction in the period analyzed; in the FFT it was -16.1%, in the Northern Arc -8.3%, in the Central Arc -19.2% and in the Southern Arc -17.7%. The spatial analysis by LISA showed that in 2019 there were clusters of high PS rates in municipalities of Acre, Mato Grosso do Sul, and Rio Grande do Sul. Clusters of CS and pregnant women living with HIV in Rio Grande do Sul, and transition areas (high-low) of AIDS in children under 5 in municipalities of Pará, Amazonas, Rondônia, and Mato Grosso do Sul, were also found. Conclusion: The study's findings reveal that MTCT of HIV and congenital syphilis persist as a major problem in Brazilian LBS and disproportionately affect women with low levels of schooling, adolescents and black women. However, its distribution is not homogeneous between the arcs, especially in the control of MTCT of HIV. There is a need to expand access to prenatal care and create mechanisms to guarantee the quality of care in general. To this end, public policies that contemplate inter-sectorial practices aimed at transforming specific social determinants of each arc and supporting binational mechanisms and agreements with legal instruments of integration are essential