Doenças Infecciosas

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Programa de Pós-Graduação em Doenças Infecciosas

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A influência da modulação por TLR2, TLR4 e TLR9 na resposta de células T reguladoras em cultura de sangue periférico de indivíduos com infecção latente pelo Mycobacterium tuberculosis, desafiadas in vitro com o bacilo de Koch
(Universidade Federal do Espírito Santo, 2018-07-10) Silva, Flávia Dias Coelho da; Rodrigues, Ricardo Ribeiro; Zeidler, Sandra Lúcia Ventorin Von; França, Johara Boldrini; Palaci, Moises; Pereira, Fausto Edmundo Lima
Latent tuberculosis infection (LTBI) affects approximately a quarter of the world's population. During LTBI, M. tuberculosis (Mtb) survives in a state of dormancy, which reactivates latent infection, which resumes normal growth and metabolism. Macrophages / monocytes (MO) play a central role in the mycobacterial pathogenesis, since they are the main cellular niche for Mtb during infections. The protective immune response, which the MO are part of is influenced by suppressive mechanisms, among them the increase of the activity of T regulatory cells (Tregs). Tregs have the ability to control tissue damage by decreasing adequate control of mycobacterial replication, and may also be involved in the reactivation and dissemination of Mtb. Toll-like receptors (TLRs) participate in the response to the infection by detecting and regulating it, and TLR2, TLR4 and TLR9 are known to recognize components of Mtb, which influence the response to kinetics and cytokine production by infection. We sought to assess the influence of TLR2, TLR4 and TLR9 agonists and antagonist in peripheral blood and Mtbchallenged whole blood cultures of individuals with LTBI (TST+ group) relative to the negative control (TST- group), investigating the frequency of Tregs and MO cells, the microbicidal activity and the dosage of cytokine IL10, IL17, TGFβ and IFNγ among these groups. Higher frequency of MO (CD14+ CD16+ HLA-DR+ , CD14+ TLR2+ HLA-DR+ , CD14+ TLR4+ HLA-DR+ , CD14+ TLR9+ HLA-DR+ ) was observed in the peripheral blood of LTBI/TST+ individuals. In the action of TLR2, TLR4 and TLR9 agonists or of TLR9 antagonist, under the frequency of Tregs cells from Mtb-challenged whole blood cultures, there was a higher frequency of these cells in the TST+ group, which was reduced after the use of TLR9 antagonist (chloroquine). As regards the influence of Mtb infection on the cultures, the microbicidal activity was lower in the TST+ group. In cultures infected with Mtb and TLRs-modulated, there was a reduction of the microbicidal activity in the TST+ group, during stimulation with TLR2 agonist, and, in the same individuals, in the stimulus with TLR9 antagonist, it was observed the restoration of the microbicidal activity. As for the dosage of cytokine in the same cultures, there was a higher production of IL10, IL17 and IFNγ in the TST+ group, especially after modulation with chloroquine, compared to the TST- group. In summary, LTBI differs from the control TST- by the higher frequency of Tregs and MO and the lower microbicidal activity, whereas the TLR9 blockade, by the use of chloroquine, resulted in the reduction of Treg cell frequency, in the higher production of IL17, IFNγ and IL10 and in the improvement of the microbicidal activity of LTBI in relation to TST-.
Abortamento humano : detecção molecular de AAV e de HPV em decídua e vilosidade coriônica
(Universidade Federal do Espírito Santo, 2007-11-14) Pereira, Christiane Curi; Vargas, Paulo Roberto Merçon de; Spano, Liliana Cruz; Miranda, Angelica Espinosa Barbosa; Oliveira, Ledy do Horto dos Santos
Pregnancy failure is a common event often of unknown cause. Some viruses are suggested as cause of abortion and, among them, adeno-associated virus (AAV), that has never been implicated as a cause of disease. AAV (AAV1-11 types), belonging to Parvoviridae family, requires helper virus function for replication, as from human papillomavirus (HPV), that belongs to Papillomaviridae family, also suggested as being an etiologic agent of abortion. Thus, this study aimed to detect nucleic acid of AAV and HPV in decidua and chorionic villi (CV) from human abortion occurred up to 22nd gestational week. A total of 118 fragments (66 decidua and 52 CV) were obtained from tissues from 81 abortion cases (68 non-intentional and 13 intentional ones). Viral DNA was extracted by DNAzolTM, TRIzolTM and/or QIAampTM DNA mini Kit methodologies and b-globina gene was amplified by PCR as a control reaction. AAV2/5 and HPV genome were amplified (nested-PCR and PCR, respectively) using primer pairs Pan1/Pan3 and Nest1/Nest2 and MY09/11, respectively. HPV positive cases were submitted to PCR-typing for the most common types (6, 11, 16, 18, 33). In situ hybridization (ISH) was developed in paraffin embedded tissues from AAV positive cases, using digoxigenin labeled probe. Frequency of AAV and HPV were observed in 28% (23/81) and 10% (8/81) of the cases, respectively. Only type AAV2 was detected. AAV2 was present in 18 and in 7 decidua and CV fragments, respectively, while HPV, in 4 and 5 fragments, respectively. AAV2 occurred in 32% (22/68) and in 8% (1/13) of non-intentional and intentional abortions, respectively, and HPV, in 10% (7/68) and 8% (1/13), respectively. Only one HPV were typed, corresponding to HPV11. ISH showed AAV DNA in 3 cases: in decidua, CV or chorionic plate and extravillous trophoblast. Co-infection rate between AAV and HPV was 26%, and with CMV (previously studied), 9%. Significant evidence of AAV infection in abortion tissues was observed in the present study, however, in lower frequency than those found in literature. Only AAV2 type revealed in the cases, instead of AAV5, suggests that it is the most frequent in population and/or shows tissue tropism. Infected cells with AAV2, observed by ISH in decidua and in extravillous trophoblast, suggest that cellular invasiveness of infected cells could be compromised and that gestational loss may occur. Frequency of HPV in CVs is in accordance to literature. HPV was found in similar frequency in the two abortion groups. AAV presence found in cases without co-infection with helper virus, could represent latency, autonomous replication or co-infection with other helper virus. These results do not allow inference to a causal association between AAV and abortion, albeit mostly detected in non-intentional abortion.
Alcoolismo e Strongyloides stercoralis : investigação de possíveis fatores associados à maior prevalência do nematoide em alcoolistas crônicos
(Universidade Federal do Espírito Santo, 2017-02-17) Ribeiro, Steveen Rios; Pereira, Fausto Edmundo Lima; Falqueto, Aloísio; Gomes, Daniel Claudio de Oliveira; Braga, Fabio Ribeiro; Leite, Gustavo Rocha
Introduction. Strongyloides stercoralis (Bavay, 1876) is an intestinal nematode that can proliferate in the host by autoinfection, and persist for decades without further exposure to exogenous infection. The prevalence of the parasite is poorly known in the state. Higher prevalence of S. stercoralis in chronic alcoholic patients than in non-alcoholics, attended at the same hospital, has been reported, but there are doubts about if there is a greater exposure to the parasite or greater survival and fecundity of females in the duodenum would increase the chance of encountering larvae in the feces. Objectives. To evaluate: (a) the prevalence of S. stercoralis in the state on samples of schoolchildren aged 7 to 14 years and samples from patients attended at the different outpatient clinics of the Hospital C.A. Moraes (HUCAM) and Hospital Concórdia at Sta. Maria de Jetibá; (b) the prevalence of the parasite on samples of alcoholics and non-alcoholics in the Department of Gastroenterology of HUCAM and Hospital Concordia; (c) the number of S. stercoralis rabditoid larvae on stools of alcoholics and non-alcoholics patients; (d) the anti-S. stercoralis antibodies on serum and Treg lymphocytes (Treg) in peripheral blood in alcoholics and non-alcoholics; (e) the use of the conventional PCR method on stool samples of alcoholic and non-alcoholic patients, to confirm the difference in prevalence observed between the two groups.
Alterações craniofaciais e tomográficas em pessoas atingidas pela hanseníase atendidas no Programa de Unidade Básica de Saúde e no Hospital Colônia Pedro Fortes, Cariacica (ES), Brasil
(Universidade Federal do Espírito Santo, 2017-04-10) Serafim, Rachel Azevedo; Deps, Patrícia Duarte; Falqueto, Aloísio; Floriano, Marcos Cesar
Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, and, more recently, Mycobacterium lepromatosis, a slow evolution, manifested mainly by dermatoneurological signs and symptoms. In addition to affecting the skin and peripheral nerves, it can also compromise the nasal tissues, eyes, testicles and bones. Skeletal facial and extremity deformities are historical markers and part of the stigma of this disease. Objective: To study craniofacial changes in leprosy. Methods: A case series study was carried out. Fifty-five patients were evaluated, 26 ex-leprosy from the Pedro Fontes Hospital and 29 leprosy patients from the UBS of Jardim América, Cariacica/ES, from September 2015 to December 2016. They were submitted to a Questionnaire with epidemiological data, otolaryngological evaluation and tomographic examination, when necessary. We attempted to correlate some variables with nasal / facial changes clinically and radiologically such as: gender, age, delay time in the diagnosis of leprosy, classification of leprosy, group of participants, leprosy face characteristics. Results: Of the main results found, ten (18.2%) patients presented features of the leprosy face, nine (16.4%) had nasal tip projection smaller than normal, 12 (21.8%) had no nasal tip support, nine (16.4%) had no nasal dorsal support, and the columella was reduced in 14 (25.5%). Regarding the tomographic findings of the 38 patients evaluated, the nasal bones were altered in nine (23.6%), there was resorption of the anterior (partial or total) nasal spine in 21 (55.2%) and septal perforation In five (13.2%), and 16 (42.1%) had lower and middle atrophy of the turbinates. In addition, between the toothed teeth (with three or more upper incisors) only one (2.6%) presented partial resorption with root exposition of the alveolar maxilla process, about upper toothless 27 (71%) presented resorption (partial or even palatal process), and 28 (73.7%) had lost all four upper incisors.
Alterações genéticas em M. tuberculosis durante a fase de infecção latente e suas possíveis implicações biológicas.
(Universidade Federal do Espírito Santo, 2022-03-09) Silva, Carlos Andre Cunha da; Palaci, Moises; https://orcid.org/0000000320136071; http://lattes.cnpq.br/2602694352713051; https://orcid.org/; http://lattes.cnpq.br/; Spano, Liliana Cruz; https://orcid.org/0000000262056988; http://lattes.cnpq.br/7451382455806895; Vinhas, Solange Alves; https://orcid.org/; http://lattes.cnpq.br/2611351220510331
Tuberculosis (TB) is humanity's oldest infectious disease, and it still represents a major challenge today. Caused by species of the Mycobacterium tuberculosis Complex (CMTB), the disease has a wide distribution, predominantly in the poorest populations and in countries with lower socioeconomic development. A major problem related to TB is latent infection, in which the bacterium is in the host in a quiescent form denominated “dormancy”. Despite recent studies breaking the paradigm of the binary model of interaction between MTB and the host, which consisted of the forms of disease (active) and latent infection (LTBI), little is known about the physiological state of MTB during the latency period. In this context, this work aims to study genetic alterations in secondary cases from their respective index cases and to investigate possible alterations and their biological implications. Bioinformatics analyzes were used in 24 strains, through comparative genomics between index cases and their respective secondary cases using RAST, Snippy and Spades software. The genetic differences that led to some modification in the secondary case were called variants or variations. Data analysis indicated that most of the variations found were in the metabolic subsystems related to virulence and membrane transport, we also found that in the subsystems related to dormancy and stress response there were no variations. There are no genetic alterations that lead to loss or gain of M. tuberculosis resistance during the dormancy period in secondary cases.
Análise da concordância de um teste rápido treponêmico com um teste VDRL com vistas ao seu emprego na triagem reversa da sífilis em gestantes durante o pré-natal no Brasil
(Universidade Federal do Espírito Santo, 2013-09-13) Degaut, Andressa Bolzan; Dietze, Reynaldo; Barros, Geisa Baptista; Miranda, Angelica Espinosa Barbosa
Introduction: The present study used information from the Sentinel Childbirth Study for 2010/2011 (Estudo Sentinela Parturientes) under the Ministry of Health as source of data. Objectives: To analyze the concordance of a rapid treponemal test with a VDRL test and with laboratory routine flow sheet testing used for syphilis diagnosis in Brazil. To assess how often the ministerial protocol recommendations for syphilis diagnosis during the mother’s prenatal and delivery periods have been complied. Methods: serum samples from 2.426 women ready to give birth were selected out of a total of 38.393, who met the criteria for blood sampling: positive results for syphilis diagnosed by means of rapid test at the time of admission in a hospital or the absence of a syphilis screening during prenatal period. These samples were sent to the study reference laboratory where the VRDL test would be carried out. In case of a positive finding, the test TPHA – study flow chart, would be carried out. The Kappa test was used to analyze the concordance between rapid and VDRL tests. The frequency of agreement between the final results of the flow chart and the rapid test performed at the maternity hospital was also calculated. The descriptive analysis of the study results also includes socio-demographic data from the women ready to give birth and information on prenatal medical consultations. Results: The rapid treponemal test presented a concordance of 83.4% (Kappa) when compared to the non-treponemal VDRL test. The rapid test was positive to 95.6% of the 298 expectant mothers who had a syphilis positive laboratory result according to the procedures used (VDRL and reagent TPHA). Of the 303 expectant mothers with a positive result for syphilis, 23.3% were between 30-39 years old; 38% were between the 5th and the 8th grade (incomplete) of middle school or its equivalent; and 51.7% were brown-skinned individuals. Most of the expectant mothers (91.7%) had prenatal tests performed; 74.3% (225) had the test 1 for VDRL, of which 41.3 had a non-reactive result. Of the 38.3% (116) expectant mothers who got the test 2 for VDRL, 36.2% had a non-reactive result. Conclusion: The rapid treponemal test presented an outstanding concordance with the VDRL test, and considering the growth in its use during the prenatal period, it can be considered as a parameter to indicate the immediate beginning of treatment for syphilis in expectant mothers. Due to the high frequency of agreement (95.6%) with laboratory results (VDRL e positive TPHA), the rapid test can improve diagnosis and treatment to expectant mothers during prenatal medical consultations, with no need to wait for the laboratory result. Considering women with a positive result at the delivery moment, we can conclude that expectant mothers are still acquiring syphilis during pregnancy. We can also conclude that the compliance of the ministerial protocols for both tests during prenatal period and at the delivery moment should be broadened. In this context, the rapid test can perform a crucial role in promoting early diagnosis for expectant mothers and provide the due treatment, aiming to reduce congenital syphilis and to break the syphilis transmission chain.
Análise da série histórica de malária residual em municípios do Espírito Santo com sistemas de Mata Atlântica no período de 2007 a 2018
(Universidade Federal do Espírito Santo, 2019-03-26) Mendonca, Gustavo Vital de; Junior, Crispim Cerutti; https://orcid.org/0000000294854191; http://lattes.cnpq.br/4257067087979999; https://orcid.org/0000-0002-4314-9708; http://lattes.cnpq.br/1083615409753183; Leite, Franciele Marabotti Costa; https://orcid.org/0000000261716972; http://lattes.cnpq.br/7170760158919766
Introduction: Malaria, for thousands of years, has remained one of the most important infectious diseases occurring in humans. It is caused by protozoa of the genus Plasmodium, being transmitted by the bite of the infected female mosquito of the genus Anopheles. The autochthonous malaria of the Atlantic Forest, or residual malaria of the Atlantic Forest systems (RSMA), is due to the presence of the bromeliads, whose whorls are used in the reproduction of the Anopheles mosquitoes of the subgenus Kerteszia. These are considered the primary vectors of both human malaria and simian malaria in this region, which raises the question of whether bromeliad malaria could be considered a zoonosis. In the first half of 2017, Brazil experienced a large outbreak of yellow fever, and up to May 31, 2017, 3,850 deaths of non-human primates were reported to the Ministry of Health, 642 of which were confirmed for yellow fever by laboratory criterion or epidemiological link. Objectives: To evaluate the impact of the yellow fever epizootic on the cases of residual malaria in the Atlantic Forest systems and to evaluate the association of climatic factors with the occurrence of malaria in the study region. Methods: A database containing the cases of autochthonous malaria recorded in the municipalities of Domingos Martins and Santa Teresa (n = 244), in the mountain region of the state of Espírito Santo, between 2007 and 2018 was developed. Analysis were performed using a Poisson regression model with the adoption of a three-month moving average. Results: The Poisson models were able to demonstrate a negative correlation between the yellow fever epizootic and the number of malaria cases. A statistically significant positive correlation was found between the number of malaria cases and the mean maximum temperature in the previous month. The adopted model presented low power of explanation given the multifactorial nature of the transmission chain. We conclude that apes play an important role in the occurrence of Atlantic Forest malaria, but their presence is not enough to explain all the aspects of the complex chain of transmission. Keywords: malaria, epidemiology, bromeliad, Poisson distribution, yellow fever.
Análise de aspectos de virulência, resistência aos antimicrobianos e diversidade genética de Staphylococcus aureus isolados de colonização nasal em puérperas
(Universidade Federal do Espírito Santo, 2024-06-22) Nilo, Ana Paula Marques Caldeira; 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; Schuenck, Ricardo Pinto ; https://orcid.org/; http://lattes.cnpq.br/; Orientador2; https://orcid.org/; http://lattes.cnpq.br/; https://orcid.org/; http://lattes.cnpq.br/; Cavalcante, Fernanda Sampaio ; https://orcid.org/; http://lattes.cnpq.br/; Palaci, Moises ; https://orcid.org/; http://lattes.cnpq.br/; 3º membro da banca; https://orcid.org/; http://lattes.cnpq.br/; 4º membro da banca; http://lattes.cnpq.br/; 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/
Nasal colonization by Staphylococcus aureus in postpartum women is relevant due to the risk of colonization of newborns and of infections in both groups. This study aimed to evaluate the colonization rate, resistance, virulence, and genetic diversity of S. aureus isolated from nasal colonization in postpartum women. Nasal swabs were collected (n = 306) within 48h after birth in the maternity ward of a hospital in Brazil, between March/2018 and March/2019. Demographic data were obtained from medical records. Antimicrobial susceptibility was determined by the disk diffusion test and Minimum Inhibitory Concentrations (MICs) were obtained by broth microdilution. Biofilm production was evaluated using a polystyrene microplate test. Polymerase Chain Reaction (PCR) was used to perform SCCmec typing and detect the following adhesin and toxin genes: fnbB, clfA, clfB, cna, bbp, hla, hld, hlg, hlg-2, lukSF-PV, lukED, eta, etb, sea, seb, sec, sed, see and tsst-1. Genetic diversity was assessed by Random Amplified Polymorphic DNA (RAPD). The rate of S. aureus nasal colonization was 14.7% (45/306), with seven (15.6%) MRSA. The overall MRSA rate was 2.3% (7/306). Demographic data demonstrated an average age of 30 years, and high rates of unemployment (66.7%), multiparity (83.3%), and comorbidities (85.7%). High resistance rates to penicillin (88.9%) and erythromycin (53.3%) were observed. All MRSA isolates carried SCCmec type IVa and one was characterized as oxacilin-susceptible methicilin-resistant S. aureus (OS-MRSA). Most isolates (84.4%) were classified as strong biofilm producers. Several virulence genes were detected and the most prevalent were hld (93.3%), hla and eta (48.9%), and sea (42.2%). RAPD analysis identified 14 profiles. Profile J grouped 11 isolates (among them, five MRSA, one OS-MRSA, and one MSSA-MDR) and was the second with the greatest diversity of virulence genes (n = 14). The study highlights the high rates of toxin genes among nasal isolates of S. aureus in postpartum women, with emphasis on the genes for exfoliative toxin A and enterotoxin A. These toxins are relevant in puerperal mastitis and severe neonatal infections. This is the first report of an OS-MRSA isolate colonizing the anterior nares of postpartum women
Análise de fatores geográficos e climáticos relacionados à distribuição de Phlebotominae (Diptera: Psychodidae) em área de transmissão de leishmaniose tegumentar americana no Estado do Espírito Santo, Brasil
(Universidade Federal do Espírito Santo, 2014-08-07) Farias, Priscila Camargo Granadeiro; Fux, Blima; Falqueto, Aloísio; Shimabukuro, Paloma Helena Fernandes; Cerutti Júnior, Crispim
American cutaneous leishmaniasis (ACL) affects the skin and mucous membranes caused by dermotropic parasites of the genus Leishmania Ross, 1903. The parasites are transmitted through the bite of small insects of the family Psychodidae, the sandflies. The municipality of Cariacica, Espírito Santo, Brazil, has been in the last five years (2009-2013) among the five municipalities which had the largest numbers of reported cases in the, according to the State Department of Health (SESA-ES, 2014). The locality of Roda DÁgua has shown high epidemiological importance, due to the large concentration of cases contributing to the municipality notifications. Evaluating the registered cases from the region, from the medical reference service, Unidade de Medicina Tropical da Universidade Federal do Espírito Santo, it was observed that they occurred up to 550 m of altitude, in an area between 20-718 m above sea level. The most likely hypothesis is that the phenomenon is related to the vector distribution, since humans and animals are be present in all altitudes. From February 2002 to January 2004 sand flies were simultaneously captured in monthly collections in Roda D’Água , at three altitude levels: level 1 - up to 250 m, level 2 - between 250 and 500 m and level 3 - above 500 m. In each level, collection of sand flies was carried out in two environments: sylvatic and peridomicile. Collections were made using modified Shannon traps and by active search with Castro pooter. We evaluated flight activity of the species as the rainfall (rainy and dry seasons) and the seasonality. Only species known to be anthropophilic and with epidemiological importance were statistically analyzed. Abundance, richness, diversity, equitability, and dminance ecological indices were estimated. A total of 13,233 sand flies from 23 species were collected. The most abundant species was Nyssomyia intermedia (61.12%), followed by Pintomyia fischeri (18.20%) and Migonemyia migonei (8.68%), all species are anthropophilic. Pintomyia monticola represented 1.67% of the total specimens collected and is also antropophilic. The other species comprised 10.10% of the total specimens collected. The altitude affected the distribution of four species, and Ny. intermedia and Pi. fischeri were more abundant at level 2, Mg. migonei most abundant at level 1 and Pi. monticola at level 3. Nyssomyia intermedia and Mg. migonei were statistically more abundant in peridomestic areas and Pi. monticola in sylvatic environment. Pintomyia fischeri occurrence was not statistically significant according to environment, but it was the only one affected by the rain and showed seasonality, most commonly found in dry periods and during the winter. Nyssomyia intermedia seems to be the most important vector of ACL in Roda D’Água and Mg. migonei presents probably acting as asecondary vector. Pintomyia fischeri does not seem to be involved in disease transmission to humans in the locallity, despite having already been incriminated in others regions. According to its distribuition, probably Pi. monticola does not play a role in ACL transmission in Roda D’Água.
Análise de transmissão e da dinâmica de modificação de genótipos de Mycobacterium turbeculosis na Região Metropolitana de Vitória-ES em um intervalo de 10 anos
(Universidade Federal do Espírito Santo, 2015-02-25) Nóbrega, Renata Lyrio Peres; Palaci, Moisés; Maciel, Ethel Leonor Noia; Oliveira, Martha Maria de; Nunes, Ana Paula Ferreira; Miranda, Angélica Espinosa Barbosa; Suffys, Philip Noel
Introduction: Molecular epidemiology have contributed to the understanding of the dynamic of transmission of tuberculosis (TB). Although many papers have been published on this subject, few studies, however, were performed taking into account the dynamic of modification of genotypic profiles of M. tuberculosis (Mtb) in a long time frame. Objective: To identify genotypes and factors associated with cluster size of Mtb in the population of the Metropolitan Area of Vitória – ES (RMV) and to analyze the dynamic of modification of Mtb genotypes in the RMV in a 10 years frame. Methods: This study had two parts.
Análise de um procedimento simplificado de coleta de escarro para avaliação da atividade bactericida precoce de fármacos contra o Mycobacterium tuberculosis
(Universidade Federal do Espírito Santo, 2011-04-26) Nascimento, Cristina Paula do; Palaci, Moisés; Conde, Marcus Barreto; Dietze, Reynaldo
In clinical trials studies on new drugs against tuberculosis, the main methodology used is the evaluation of the early bactericidal activity (EBA), which quantifies the decrease of CFU of Mycobacterium tuberculosis in sputum samples during the first 2 days of treatment, through 12 to 16 hours of nocturnal sputum collections. However, the sputum collection for a period of 12 to 16 hours has several shortcomings. In this context, we proposed to develop and evaluate a simple, less time-consuming procedure for sputum collection that does not require hospitalization and presents the same efficiency as a 12-hour collection procedure. We performed quantitative cultures of sputum to measure the bacterial load after three different procedures: 5-hour and 12-hour sputum collections. So this study was divided into two stages. In the first step, the bacillary loads observed in sputum were compared to those obtained after a 5-hour (6,17 log10CFU/mL) and 12 hour (6,23 log10CFU/mL) collection, and there was no statistically significant difference (p =0,27). For the second stage, the patients underwent 4 procedures for sputum collection on consecutive days - two 5-hour collections and two 12-hour collections, in order to analyze the bacterial load variation intra and inter-patients. When the intra-patient variation in the bacillary load was compared between the procedures lasting 5 hours (0,037 Log10CFU/mL) and 12 hours (- 0,022 Log10CFU/mL), no statistically significant difference was observed (p = 0,56). Moreover, the morning collection has reduced the inter-patient variation and improved the accuracy for estimation of the average change in bacterial load from a collection of one day to the other (standard error for 5-hour =0,019 and standard error for 12-hour =0,028). These results show that a 5-hour morning sputum collection is as representative as that provided by a 12-hour overnight collection. In conclusion, the simplified procedure of sputum collection for a period of 5 hours proposed by this study could be used in clinical assessment of EBA as an alternative to 12-hour collections, with no impairment to the EBA evaluation of the study drug.
Análise de virulência e ação de antimicrobianos terapêuticos e potenciais antimicrobianos em células planctônicas e em biofilme de Escherichia coli enteroagregativa: um estudo in vitro e in vivo
(Universidade Federal do Espírito Santo, 2022-11-01) Guerrieri, Caroline Gastaldi; Spano, Liliana Cruz; https://orcid.org/0000000262056988; http://lattes.cnpq.br/7451382455806895; https://orcid.org/0000-0002-6230-7695; http://lattes.cnpq.br/7158387702645384; Sa, Marta Helena Branquinha de; https://orcid.org/0000-0002-9752-8148; http://lattes.cnpq.br/2158584413298259; Schuenck, Ricardo Pinto; https://orcid.org/0000000198255762; http://lattes.cnpq.br/1211608551542058; Nunes, Ana Paula Ferreira; https://orcid.org/0000-0001-7919-2938; http://lattes.cnpq.br/7851528667690358; Pereira, Marcos Dias
Enteroaggregative Escherichia coli (EAEC) is characterized by heterogeneity of potential virulence factors and biofilm formation. It can be classified as typical (tEAEC) and atypical (aEAEC) based on the presence of the AggR regulon, suggesting a higher virulence for tEAEC. As a result of its remarkable heterogeneity, its identification and determination of the susceptibility profile are not performed in the routine of laboratory diagnosis, and its treatment is done empirically. In addition, biofilm formation, which leads to the occurrence of persistent infections that may require antimicrobial therapy, confers resistance to antimicrobials and, in most cases, makes their eradication impossible. Therefore, the development of new therapeutic strategies for EAEC infections, mainly associated with biofilm formation, is sorely necessary. Phendione and its metallic derivatives (Ag-phendione and Cu-phendione) have shown effectiveness against several microorganisms, but so far their activity in E. coli isolates has not been investigated. Given the above, we aimed to analyze in vivo aspects of EAEC virulence and to analyze in vitro and in vivo the action of classic and new antimicrobials (phendione and its derivatives) on planktonic cells and EAEC biofilm. Regarding virulence analyses, we evaluated the survival of larvae after inoculation of the EAEC 042 wild-type and its AggR mutant. To evaluate the combination therapy with classic antimicrobials, the biofilm was formed in a peg-lid system, treated with combinations of antimicrobials from different therapeutic classes, and the inhibition and eradication potential of each combination was determined. We also analyzed the activity of phendione-derived compounds for EAEC in the planktonic form by determining the minimum inhibitory concentration (MIC) and evaluating combinations of compounds with antimicrobials for resistant strains using checkerboard and time-kill methodologies. We also investigated the anti-biofilm activity of the compounds by determining the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC), in addition to other aspects such as the ability to inhibit the formation and disarticulate the mature biofilm and the possibility of using compounds associated with classic antimicrobials as a combined therapy to biofilm inhibition and eradication. Finally, we tested the treatment with Cu-phendione and Ag-phendione and their association with ampicillin in vivo in the G. mellonella model. Regarding the virulence of EAEC, we observed that the EAEC 042 mutant AggR strain showed a significant reduction in the mortality of inoculated larvae in relation to the wild-type strain, but its virulence was not completely lost. Combination therapy of classic antimicrobials in EAEC biofilms led to the eradication of 50% of the tested strains (2/4) in the ciprofloxacin-ampicillin and ciprofloxacin-tobramycin combinations. Phendione and its metal complexes showed high activity against EAEC strains in planktonic form with low MIC value, and, combining the metal complexes with antimicrobials by the checkerboard method, we observed an additive effect in most combinations. On the other hand, in time-kill experiments, the compounds showed synergism with both tetracycline and ampicillin. Regarding anti-biofilm activity, Cu-phendione showed the best result in the biofilm inhibition and eradication (68.6% - 24/35 strains), in the disarticulation of the mature biofilm (IC50 = 1.87 μM) and the inhibition of biofilm formation, mainly after six hours of incubation. Evaluating combination therapy in biofilms, we observed biofilm eradication of all strains (4/4) in combinations of Cu-phendione with cefoxitin, tobramycin, tetracycline, and ciprofloxacin, and in combinations of Ag-phendione with tobramycin and ciprofloxacin. Furthermore, the combination of ampicillin with Ag-phendione significantly increased the survival of G. mellonella larvae when compared to ampicillin administered alone. In conclusion, the results obtained here demonstrate that the in vivo virulence of EAEC seems to be related to the AggR regulon, but not exclusively. Regarding the treatment strategies for EAEC infections associated with biofilm formation, despite the combination therapy with two classic antimicrobials having presented better results than the treatment with antimicrobials alone, analyzed in a previous study, the phendione-derived compounds were more promising, especially for its ability to eradicate the biofilm either alone or in association with antimicrobials.
Análise do perfil de imunossenescência em células T de pacientes em diferentes estágios de infecção por SARS-CoV-2
(Universidade Federal do Espírito Santo, 2022-08-12) Sarmento, Isabela Valim; Gomes, Daniel Claudio de Oliveira; http://lattes.cnpq.br/3965075540969796; https://orcid.org/0000000322719190; Silva, Eduardo de Almeida Marques da; Palaci, Moises; https://orcid.org/0000000320136071; http://lattes.cnpq.br/2602694352713051; Tadokoro, Carlos Eduardo; https://orcid.org/0000000278745657; http://lattes.cnpq.br/9447506269190990
COVID-19 is a disease caused by SARS-CoV-2 that affects the respiratory system, causing lung damage that can progress to severe acute respiratory syndrome (ARDS), acute increase in inflammatory cytokines (cytokine storm), hepatic, cardiovascular, and renal damage. An exacerbated inflammatory environment, as seen in COVID-19, can lead to changes in the profile of differentiation and functionality of T cells. These factors promote the expansion of senescent T cells, which is defined by the progressive loss of costimulatory receptors (CD27 and CD28), DNA damage, p38 MAPK activation, and loss of proliferative capacity. The accumulation of senescent T cells has been associated with the immunopathogenesis of many diseases. However, it is still poorly understood in the context of COVID-19. This work evaluated the clinical/laboratory profile of patients with COVID-19, clinically classified between oligosymptomatic, moderate, and severe. In addition, we evaluated senescent phenotype characteristics in T cell compartments. Our results demonstrate alterations in several laboratory parameters such as leukocytosis, neutrophilia, eosinopenia, monocytosis, lymphopenia, increased LDH, direct bilirubin, triglycerides, C-reactive protein, urea, and creatinine. In addition, patients with COVID-19, especially the severe and moderate groups, showed changes in blood gas with disturbances in arterial pH and PCO2. Our phenotypic analyses showed a decrease in cell viability in the groups most affected by the disease (moderate and severe), with changes in the frequencies of CD4+ and CD8+ T cells, increased DNA damage identified by γH2Ax phosphorylation, as well as increased expression of MAPK p38 that is linked to senescence. Furthermore, compared to the oligosymptomatic group, critically ill patients showed an accumulation of highly differentiated populations, identified by the CD28-CD27- and terminal memory cells (T EMRA) subgroups. Thus, patients with the most severe shape of COVID-19 exhibit a senescent T-cell phenotype, which may be one of the aggravating factors for this disease.
Análise do potencial preditivo de marcadores de exaustão celular como indicadores de sucesso da resposta terapêutica antituberculose em pacientes com tuberculose pulmonar ativa
(Universidade Federal do Espírito Santo, 2016-07-01) Portela, Bruna Sousa de Mendonça; Gomes, Daniel Cláudio de Oliveira; Santos, Eduardo Caio Torres dos; Rodrigues, Rodrigo Ribeiro
Tuberculosis (TB) infection caused by Mycobacterium tuberculosis (Mtb) continues to represent a serious risk to public health. Current treatment routines require long period of care and also are toxic, which often lead to low adhesion and increase of multidrugresistant strains. Infectious processes that result in antigen persistence or even chronic inflammatory syndromes affect the effector function of antigen-specific T cells reducing its ability to proliferate and to produce inflammatory mediators and develop the cytotoxic functions. The phenomenon described as cell exhaustion, which is characterized by a high expression of PD-1, TIM-3, CTLA-4 and KLRG-1 receptors has been described as the main mechanism involved in this immune deactivation. In addition, the severity of infections caused by pathogens such as HIV, HBV and HCV are correlated with increased expression of these markers, which suggest their association in the pathogenesis and also indicate a potential target as predictive marker of immunologic/therapeutic efficacy. In this work we aimed to evaluate the expression of the cell exhaustion receptors PD-1 and TIM-3 as a potential target for therapeutic efficacy during chemotherapy against active pulmonary Tuberculosis. We showed higher frequencies of PD-1 and TIM-3 in patients with TB and the consequent loss the expression after treatment initiation. Moreover, we observed an significant increase of IFN-ɣ and decreased IL-10 production, which directly reflected on the microbicidal capacity observed in the whole blook killing assay. Additionally a positive correlation between TIM3+ and PD1+TIM3+ expression in CD8 T cell and bacillary load was observed indicating a possible association of this receptor to clinical evolution. Our results extend the knowledge for development of new strategies in predictive diagnosis and therapeutic efficacy for TB, which may be exploited to elimination of tuberculosis.
Análise do tratamento da infecção latente pelo Mycobacterium tuberculosis na faixa etária de 0 a 15 anos nos programas de referências para tuberculose nos municípios da Grande Vitória/ES-Brasil
(Universidade Federal do Espírito Santo, 2012-06-29) Gomes, Sandra Mary Jardim; Maciel, Ethel Leonor Noia; Hadad, David Jamil; Miranda, Angelica Espinosa Barbosa; Alves, Rosana
Controling of Tuberculosis (TB) one of the measures used in Brazil is the treatment of latent infection by Mycobacterium tuberculosis (ILTB), which is made in the TB Control Program (PCT). The evolution of the infection to disease during the life is estimated at 5-10% related to immunocompetent adult, however, in child is estimated 43%.This research was an observational and analytical study, which aimed to analyze the epidemiological profile and factors related to renunciation of treatment for ILTB. Individuals were analyzed until 15 years old who were undergoing treatment for ILTB, in the PCT of the priority municipalities of Vitória, Vila Velha, Serra and Cariacica, which are the sites that used the notification form of treatment for ILTB. The form was used as a tool for data collection. The research period was between July 2009 and August 2010. 144 individuals were found in treatment for ILTB, and 140 (97,22%), the majority of nomination was TB contacts, 46 (31.94%) abandoned the treatment, and 98 (68.06%) completed the treatment. Most individuals were contacts of TB, and when was analyzed the situation of the bacilloscopy (BAAR) of the index case of contact, the majority of both the group that left, and the group that completed treatment, 97,62% e 87,91% (p=0,06), respectively, were positive. Regarding the type of contact, the home was the most frequent, and also between the two groups, both those abandoned and those who completed, totaled 81,82% e 84,21% (p=0,72), respectively, followed by others, who were uncles, grandparents , who lived nearby. Children and teenagers were evaluated mostly had scar of BCG (Bacillus of Calmette and Guérin) present, and had mostly a normal chest X-ray. Teenagers (≥ 10 years old), were checked if they had more chances to leave the treatment of ILTB, comparing with less than 10 years old, because the same need caregivers help for use of medication, however, the majority of both groups, concluded the treatment, teenagers 75% and children 64,13% (p=0.17). This study reinforces the need to control the contacts of patients, identifying priority children and teenagers and developing strategies for treatment adherence. The study can also stimulate the improvement of notification s system since, despite the orientation of MOH, its implementation has not yet been standardized
Análise dos custos médio e por atividade do teste SCOT-TB para o diagnóstico da tuberculose pulmonar em laboratórios públicos
(Universidade Federal do Espírito Santo, 2023-08-25) Segatto, Isabella Recla; Palaci, Moises; https://orcid.org/0000000320136071; http://lattes.cnpq.br/2602694352713051; https://orcid.org/0009-0003-3220-9300; http://lattes.cnpq.br/6833518803534605; Teixeira, Carlos Graeff; https://orcid.org/0000000327250061; http://lattes.cnpq.br/0464152494769261; Miranda, Silvana Spindola de
The laboratory diagnosis for the investigation of tuberculosis (TB) through culture and the identification of the Mycobacterium tuberculosis resistance profile by the antimicrobial susceptibility test (AST) is essential for disease control. However, the high costs and complexity of conventional methods for conducting these tests have reduced their availability through the Brazilian public healthcare system (SUS). In this context, facilitating access to diagnosis requires the adoption of new tests with easy operational methodologies and affordable costs. Prior to the adoption of new technologies for TB diagnosis, it is necessary for public health managers to perform economic evaluations comparing the costs of conventional Technologies to innovations. This study aimed to evaluate the average cost and activity-based cost (ABC) of the Swab Culture Optimized Test (SCOT-TB) test for the diagnosis of pulmonary tuberculosis in public laboratories with different levels of infrastructure and biosafety complexity. The cost analysis was based on two methods: average cost and ABC. The SCOT-TB phenotypic test, developed by researchers from Nucleus of Infectious Diseases of the Federal University of Espírito Santo (NDI-UFES), detects growth, identifies, and determines the sensitivity of the TB bacillus to isoniazid and rifampicin from sputum samples. The costs of SCOT-TB were compared to those of the BD BACTEC MGIT 960® test (MGIT), the gold standard method for culture and AST, conducted at the Laboratory of Mycobacteria Research at the Faculty of Medicine of the Federal University of Minas Gerais (LPM/FM/UFMG), classified as biosafety level 3 (BSL 3), and at the Laboratory of NDI-UFES, classified as biosafety level 2 (BSL 2). At LPM/FM/UFMG, the results for average cost and ABC were respectively U$15.84/U$11.81 for SCOT-TB and U$20.59/U$14.25 for MGIT-culture. At NDI/UFES, the results for average cost and ABC were respectively U$16.84/U$10.99 for SCOTTB, U$26.74/U$15.82 for MGIT-culture, and U$50.15/U$33.16 for MGIT-AST. Additionally, our results demonstrated that for all tests, the cost component with the highest contribution to both ABC and average cost was the input. Infrastructure, on the other hand, had the least impact on costs for all tests, noting that for the ABC of SCOTTB, it was not relevant for either the BSL3 or BSL2 laboratory. Based on these findings, our study demonstrate that the SCOT-TB test reduces both the average cost and ABC of the diagnosis of pulmonary tuberculosis when compared to the standard method, BD BACTEC MGIT 960®, in all evaluated laboratories, regardless of the biosafety level.
Análise dos óbitos por AIDS no Brasil e sua relação com o uso de terapia antirretroviral no período de 2009 a 2013
(Universidade Federal do Espírito Santo, 2016-04-06) Freitas, Marcelo Araújo de; Pascom, Ana Roberta Pati; Miranda, Angélica Espinosa Barbosa; Mesquita, Fábio Caldas de; Cerutti Junior, Crispim
INTRODUCTION: Despite the introduction of universal access to antiretroviral therapy (ART) in Brazil 20 years ago, around 12,000 people still die of AIDSrelated causes every year. The aim of this study was to describe antiretroviral treatment of people living with HIV (PLHIV) who died of AIDS-related causes between 2009 and 2013. METHODS: We conducted a cross-sectional, populationbased study to establish the distribution of AIDS-related deaths among PLHIV between 2009 and 2013 in Brazil according to antiretroviral therapy status. Data were generated from a linkage process between Mortality Information System (SIM) and National ART dispensing database (SICLOM). Trends were modeled using linear regression analysis. RESULTS: A total of 61,425 AIDS-related deaths were registered in Brazil between 2009 and 2013. Median age at death was 41 years (IQR: 33-49) and 65.7% (40,337) of deaths were among men; 47.2% (29,004) of PLHIV who died during the study period never started treatment, 7.0% (4,274) had discontinued treatment, 15.9% (9,775) were on ART for six months or less and 29.9% (18,372) were on ART for more than six months. Only 1.3% of the PLHIV were on third-line ARV regimens at the time of death. CONCLUSIONS: Almost all of those who died of AIDS-related causes in Brazil did not get the full benefit of antiretroviral therapy. Even in a context of universal access to antiretroviral treatment for many years, robust health policies targeting gaps in HIV continuum of care are crucial to further reduce the impact of AIDS-related mortality in Brazil.
Análise espacial da transmissão de genotipos de Mycobacterium tuberculosis em Vitoria, ES-Brasil
(Universidade Federal do Espírito Santo, 2015-02-26) Ribeiro, Fabíola Karla Corrêa; Maciel, Ethel Leonor Nóia; Palaci, Moisés; Suffys, Philip Noel; Oliveira, Martha Maria de; Falqueto, Aloísio; Spano, Liliana Cruz
Background. Genotyping Mycobacterium tuberculosis isolates allows study of dynamics of tuberculosis (TB) transmission, while geoprocessing allows concomitant spatial analysis of clinical and epidemiological data. In the present study, genotyping data and spatial analysis were combined to characterize TB transmission in VitóriaES-Brazil to identify distinct neighborhoods and risk factors associated with recent TB transmission. Methods. From 2003 to 2007, 503 isolates were genotyped by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping. The spatial analysis included Kernel density estimation (KDE), k-function analysis on predicted estimates from a random-effects logit model and a t-test distance analysis. M. tuberculosis isolates belonging to identical RFLP patterns (clusters) were considered to represent recent TB infection (cases). Results. Of 503 genotyped isolates, 242 (48%) were categorized into 70 distinct clusters belonging to 12 RFLP families. The overall proportion of recent transmission was 34.2%. Kernel density maps indicated three areas of most intense concentration of cases. K-function analysis of the largest RFLP clusters and families showed that both co-localized in space. The distance analysis confirmed these results and also showed that unique-pattern strains (controls) randomly distributed in space. A logit model with random neighborhood effects was used to evaluate univariate and multivariate associations. When the predicted probabilities for each neighborhood were mapped, they identified the neighborhoods with high risk for recent transmission. Conclusions. Spatial and genotypic clustering of M. tuberculosis isolates revealed ongoing active transmission of TB caused by a small subset of strains in a subset of neighborhoods of the city. Such information provides an opportunity to target TB transmission control, such as through rigorous and more focused contact investigation programs.
Análise espacial de coinfecção TB/HIV em microrregiões do Brasil de 2007 a 2011
(Universidade Federal do Espírito Santo, 2017-05-16) Loriato, Karina Covre; Miranda, Angélica Espinosa Barbosa; Cerutti Junior, Crispim; Zandonade, Eliana
Introduction: Human immunodeficiency virus (HIV) infection is an important risk factor for tuberculosis (TB). Knowledge of the spatial distribution and dependence of tuberculosis and HIV/AIDS cases in Brazil will allow the visualization of its geographical distribution and the frequency of occurrence of coinfection in space/time. Objectives: To characterize the demographic and clinical aspects of the cases of TB/HIV/AIDS coinfection and to analyze the spatial dependence of epidemiological data on these cases in the micro-regions of Brazil with the use of geoprocessing tools. Methods: The study comprises 558 micro regions of the Brazilian territory. It is an ecological study in which the SINAN tuberculosis notification database was used. Demographic and clinical epidemiological profile was performed. For the spatial analysis, the Moran index, local empirical bayesian estimator (LEbayes), the global empirical Bayesian estimator (GEbayes) and the Poisson model were used. Results: The final sample of the study was 33,773 notifications of new cases of tuberculosis in HIV/AIDS patients. In the profile, 23,621 individuals (69.94%) were male; 15,882 (54.46%) were declared black or brown; 19,216 (56.9%) were aged 15 to 39 years; and 10,484 (41.09%) had between one and three years of study. Regarding clinical aspects, 24,654 (84.71%) had suspected X-ray of TB and sputum smear microscopy was positive in 12,194 (51.11%) collected samples. The most common form of tuberculosis was pulmonary tuberculosis, in 21,100 (62.5%). Cure was reported in 17,288 (53.93%) cases, abandonment occurred in 4,575 cases (14.27%) and 5,340 (16.65%) died. The Moran index showed a weak and significant spatial correlation, being the index value 0.265481 and p-value of 0.01. Conclusions: The results showed that TB/HIV/AIDS coinfection occurs mainly in men aged 15-39, browns and blacks with up to six years of study, and does present an weak overall pattern of dependence in space.
Análise espaço-temporal dos casos de chikungunya no Espírito Santo entre 2018 e 2020: um estudo dos fatores associados
(Universidade Federal do Espírito Santo, 2023-10-24) Clipes, Marcus Vinícius Salvador; Cerutti Junior, Crispim; https://orcid.org/0000000294854191; http://lattes.cnpq.br/4257067087979999; https://orcid.org/0009-0005-6925-0272; http://lattes.cnpq.br/2449228239599129; Teixeira, Carlos Graeff; https://orcid.org/0000000327250061; http://lattes.cnpq.br/0464152494769261; Jabor, Pablo Medeiros; http://lattes.cnpq.br/1542876666875683
Introdução: Chikungunya (CHIK) is a febrile illness caused by the Chikungunya virus (CHIKV), a global-wide distributed Alphavirus. The transmission of CHIKV occurs by the bites of female Aedes vector mosquitoes. CHIK was first evidenced and identified in 1953 in Tanzania. In Brazil, there have been autochthonous cases reported since 2014. Clinically, CHIK manifests itself by intense and sudden fever, followed by fatigue, headache, skin rash, and arthralgia, which can last for weeks to months, with consequences regarding public health and the quality of life for those affected. Although mortality is low, there are substantial morbid effects related to the disease. An understanding of the social and environmental determinants related to CHIK is crucial to establish disease control and mitigation strategies. Objective: This study aims to describe the social and demographic characteristics of individuals affected by Chikungunya (CHIK) in Espírito Santo state, evaluating their association with the disease incidence. Methods: We performed a cross-sectional study to describe temporal, spatial, and sociodemographic data of individuals with a confirmed diagnosis of CHIK in Espírito Santo state, Brazil, from 2018 to 2020. The analysis included monthly incidence calculation. The data processing regarding the annual spatial distribution resulted in the construction of maps disclosing the relative risks by each municipality and the distribution of clusters. Statistical analysis through the chi-square test indicated associations between sex, race, education, and age with the disease occurrence. Results: During the period and through the area analyzed, a CHIK epidemic occurred in 2020, with 2,198.2 cases per million inhabitants incidence. Southern and central regions harbored a risk five times higher than the others in the epidemic region. Women (odds ratio - OR 1.65; 95% Confidence Interval - CI 1.58- 1.72), afro descendants (OR 1.22; 95% CI 1.13-1.33), individuals with less than 11 years of education (OR 1.48; 95% CI 1.37-1.61), and elders (OR 7.49; 95% CI 6.53- 8.59) had the highest risk for the disease occurrence, a difference statistically significant. Conclusion: CHIK stands as an emerging public health problem in Brazil since its introduction in 2014. The population susceptibility and the broad vector distribution facilitate the virus dispersion through the country’s territory. Espírito Santo suffered a substantial epidemic in 2020, possibly related to outbreaks in neighboring 12 states. The population under risk should be prioritized in health care, considering the morbidity potential of the disease.

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