Teses em Doenças Tropicais (Doutorado) - PPGDT/NMT

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/3560

O Doutorado Acadêmico em Doenças Tropicais iniciou em 2007 e pertence ao Programa de Pós-Graduação em Doenças Tropicais do Núcleo de Medicina Tropical (NMT) da Universidade Federal do Pará (UFPA).

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Diagnóstico situacional e operacional das ações de controle da hanseníase em município hiperendêmico do maranhão
(Universidade Federal do Pará, 2023-06-16) GORDON, Ariadne Siqueira de Araujo; BARRETO, Josafá Gonçalves
INTRODUCTION: Limitations for the proper implementation of leprosy control actions (LCA) in states and municipalities can strongly contribute to the perpetuation of Mycobacterium leprae transmission in their communities. Thus, constant monitoring of local leprosy control programs seems to be essential for identifying weaknesses, performance and implementing solutions. OBJECTIVE: To conduct a situational and operational diagnosis of leprosy control actions in a hyperendemic municipality in Maranhão. METHOD: Exploratory, analytical, ecological study, with qualitative and quantitative research approach. Developed in the municipality of Imperatriz, covering the teams of the family health strategy (FHS), professionals linked to the leprosy control program, individuals notified with leprosy in the period from 2001 to 2020. Data from the Notifiable Diseases Information System (SINAN) were collected and analyzed. The cases were georeferenced and analyzed to identify spatial clusters. The home addresses of notified cases were georeferenced and analyzed to identify spatial clusters. The FHS territories were also georeferenced to produce digital maps of the coverage areas. These results guided an active search among contacts of index cases and students from two municipal public schools. RESULTS: After evaluating the ACH in the city through the LEM, it was identified that the Basic Health Units (BHU) do not act as recommended for the evaluation of people affected by the disease, causing difficulties in making a diagnosis and initiating treatment. From 2001 to 2020, 6,726 cases were reported in the municipality of Imperatriz, 5,842 were georeferenced (90.8%). The spatial distribution pattern of the cases was heterogeneous with the formation of statistically significant clusters. The distribution of cases by BHU identified that 13.99% of all cases in the period were identified by a BHU. Until 2020, the municipality of Imperatriz had 41 FHS teams in the urban area of the municipality, which represented 60% of FHS coverage. The coverage area of 39 teams (95%) was georeferenced. The analysis indicated that individuals residing in a discovered area by the FHS are 14% more likely to be diagnosed with multibacillary (OR: 1.14; 95%:1.05-1.32; p=0.04) and 40% more chance of having chronic grade 2 disabilities at diagnosis (OR: 1.40; 95% :1.07-1.84; p=0.01). It was observed that over the years the chance of occurrence of multibacillary cases increased (year 2002: OR: 1.67; 95%:1.14-2.44; p<0.001; year 2019: OR: 8.06; 95%:4.86-13.36; p<0.001). The active search action resulted in three (17.6%) diagnoses of relapses among the index cases, 17 (25.3%) new cases among their household contacts and nine (12.3%) new cases among the students. CONCLUSION: Despite the high number of diagnoses carried out by the municipality, the present study identified weaknesses that result in relevant hidden endemic disease. The desired control of leprosy as a public health problem will not be achieved before the effective diagnosis and treatment of current cases that have not yet been identified. Case detection would increase significantly if the fight against leprosy was adequately carried out by the health system.
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Avaliação do hemograma, da velocidade de hemossedimentação (VHS) e da proteína C reativa (PCR) como preditores diagnósticos da síndrome febril de caráter infeccioso
(Universidade Federal do Pará, 2022-02-22) RAMOS, Francisco Lúzio de Paula; RODRIGUES, Anderson Raiol
Fever is the oldest and most frequent sign/symptom in the entire field of medicine. It is present in all ages and comprises all medical specialties. Currently, are known more than 200 causes of fever, being the etiology infectious the most common. The fever can be short term – more related to viral etiology -, and long-term, more frequently caused by bacteria, protozoa and, fungi. When excessively prolonged, it is more linked to structural factors, such as autoimmune diseases and neoplasms. The extension of etiology poses fever as a challenge most of the time. The hemogram, in turn, is the most requested exam in the medical routine due to its wide utility, since it can provide more than 20 parameters for analysis, enabling to perform a broad clinical evaluation and monitor the evolution of cases. Hemogram is very useful in the assessment of fever syndrome, as it shows a reactional state in response to infectious diseases, mainly if added to the evaluation of inflammatory tests, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This study aimed to evaluate the application of the hemogram, ESR and CRP combined with clinical-epidemiological factors and time of illness as diagnostic predictors of infectious fever syndrome. We evaluated 319 patients with fever syndrome of infectious origin, being 77 of bacterial causes, 113 of viral causes, and 129 parasitic etiology, aged between 18 and 60 years old, who were attended at the Unified Medical Care Sector of Evandro Chagas Institute, between the period from 02/2018 to 01/2020. Another 213 healthy individuals were included in the study as control group. For data analysis, we used Microsoft Office Excel (2007), Biostat 5.0 (2007), SPSS Statistics 17.0 (2010), GraphPad Prism 9.0.0 Release Notes (2020), and Rv 3.5.2 (2018) software. We applied the Odds ratio (OR) to assess chances; Kruskal-Wallis for variance; Youden index for the cutoff points between variables, and ROC curve (AUROC) for accuracy. The p-value < 0.05 was considered statistically significant. The results revealed that the bacterial diseases have as characteristics in hemogram the increase in the number of neutrophils, which reflects in the numerical increase of leukocytes; In contrast, the viral diseases are characterized by the numerical reduction of lymphocytes, mainly of neutrophils, with reflection on the total number of leukocytes defined as leukopenia; the parasitic diseases assumed an intermediate profile between bacterial and viral, marked by the numerical normality of white blood cells, thus resembling the control group. However, the mean of lymphocytes was higher than in the other diseases, including the control group. In general, in bacterial diseases, there is an increase in ERS, and especially in CRP, which are also increased in parasitic diseases; but in viral diseases, these tests tend to be numerically normal, being similar to the control group in this aspect. Therefore, the inflammatory tests are increased in bacterial and parasitic diseases, but mainly in the first-mentioned, and are normal in viral diseases. Diseases such as malaria, visceral leishmaniasis, typhoid fever, HIV, and Epstein-Barr virus infections can be identified by findings peculiar to them observed in hemogram. We concluded that the numerical values of the hemogram, as well as the levels of ESR and CRP, combined with clinical and epidemiological factors and to the time of illness can predict groups of diseases and even predict specific diseases causative of infectious fever syndrome.
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Contribuição ao conhecimento do escorpionismo e do escorpião Tityus obscurus Gervais, 1843 (Scorpiones: Buthidae), de duas regiões distintas no Estado do Pará na Amazônia brasileira
(Universidade Federal do Pará, 2014-03-21) PARDAL, Pedro Pereira de Oliveira; VIEIRA, José Luiz Fernandes; ISHIKAWA, Edna Aoba Yassui
Introduction: Tityus obscurus Gervais, 1843 (Scorpiones: Buthidae) is a senior synonymous of T. paraensis Kraepelin, 1896 and T. cambridgei Pocock, 1897. It is widely distributed in the Brazilian Amazon basin and is considered the most important species responsible for scorpion stings. There were several differences in the clinical manifestations of envenomation by this species. Objective: To contribute for the knowledge of scorpionism by T. obscurus in Brazilian Amazon. Methods: We describe and compare the clinical and epidemiological findings of envenomation by T. obscurus in eastern and west areas of the state of Para. The composition of the venom, morphometric measures and DNA analysis of specimens captured were also compared between study areas. Results: From Jan 2008 to Jul 2010 were included 48 patients with confirmed envenomation by T. obscurus. Most of them came from the eastern region (70.8%). Median age groups were similar in both areas. Most scorpion stings took place during the day and occurred significantly on the upper limbs. The time between the sting and admission to the health center was less than three hours in both areas. Most eastern patients had local manifestations while in the west, systemic manifestations predominated. Local symptoms were similar in both areas, but systemic signs and symptoms were more common in the west. Symptoms frequently observed at the sting site were local and radiating pain, paresthesia, edema, erythema, sweating, piloerection and burning. The systemic manifestations were higher in patients from the west. Furthermore, neurological symptoms, such as general paresthesia, ataxia, dysarthria, myoclonus, dysmetria, and electric shock-like sensations throughout the body were reported only by patients from the west. Mitochondrial gene 16S rRNA showed a polymorphism of 9.06% with divergence from 9.7 to 11% forming two distinct at Neijgbor-Joining and Máxima Parcimônia. There were 18 and 20 specimens captured in west and in eastern regions, measuring between 62.15 to 85.24mm. The largest specimens were captured in the west. Multivariate analysis showed a significant difference between specimens from both sites. The analysis of venom by mass spectrometry and high performance liquid chromatography showed significant differences in both the composition and concentrations of venom components. The venom of specimens captured in west showed a high concentration of compounds with affinity for K+ and Na+ channels. Conclusion: There are a regional diversity in several aspects of envenomation by T. obscurus Gervais, 1843, in the state of Para. The geographical separation promotes, probably, a speciation of specimens, forming two distinct lineages, with 16S rRNA divergences and different length, chemical composition of venom and clinical manifestations of envenomations. The authors suggest a taxonomic review of this species.
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Estimativas da dose e dos parâmetros farmacocinéticos da cloroquina em pacientes com malária por Plasmodium vivax na amazônia brasileira
(Universidade Federal do Pará, 2019-10-07) FERREIRA, Michelle Valéria Dias; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/0000-0003-4842-8762
Malaria caused by Plasmodium vivax is still an important public health issue in the Brazilian Amazon basin, with 169,000 cases recorded in 2018. The treatment is based on the concurrent administration of chloroquine and primaquine. Despite the efficacy and tolerability over 60 years of use, there are several issues related to chloroquine uses that should be elucidated in the Brazilian Amazon. The aims of the present study were to estimate the doses administered and to assess the pharmacokinetics parameters of chloroquine by a no-compartmental approach associating with patients age and gender. A prospective study of cases was carried out in the municipality of Anajas, PA, with 161 patients diagnosed with malaria caused by P. vivax, 81 children and 80 adults. The geometric mean of parasites at admission were 2,644 in children and 1,210 per mm3 of blood in adults. Parasites were cleared from the peripheral blood within 28 days. The doses of chloroquine administered ranged from 20,2 to 28,9 mg/kg in children and 16,3 to 34,09 mg/kg in adults. The proportions of patients with chloroquine doses below 25 mg/kg ranged from 29,4% to 63,6% in children and 59% in adults. The required doses were lower than the given doses in ages ranges of 4-8 years (U=64; p=0,007), 9-11 years (U=32; p<0,001) and 12-14 years (U=18; p<0,0001). Blood chloroquine concentrations in 168h in ng/ml ranged from 107 to 440 in children and 201 to 582 in adults. Blood levels of desethylchloroquine ranged from 167 to 412 in children and 178 to 482 in adults. The pharmacokinetics parameters derived from no-compartmental approach were elimination rate constant, area under the curve at day 28, extrapolated to infinite, maximum concentration, total clearance, elimination half-life, volume of distribution and meantime of residence. Overall, the data were similar to those found in other population groups and confirmed the high elimination half-life and a large volume of distribution of the drug. There was no significant influence of gender, but the age decreased significantly the clearance and the volume of distribution. The results permit to conclude that chloroquine is yet effective in the research area. Most of the patients received sub-doses of chloroquine. The pharmacokinetics parameters were not influenced by gender, but the age promoted a significant decrease in the volume of distribution and in the clearance, with the lower values in children.
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Monitorização terapêutica de fármacos utilizados no tratamento da tuberculose no Brasil
(Universidade Federal do Pará, 2018-12-07) ALBERIO, Carlos Augusto Abreu; VIEIRA, José Luiz Fernandes
Tuberculosis continues to be a public health problem throughout Brazil. Several efforts have been made to increase their cure rates, such as the use of the DOTS strategy (Directly Observed Treatment for Short Term) to reduce cases of abandonment and improve adherence to treatment. As a result of the increase in primary resistance to isoniazid, the Ministry of Health modified the therapeutic regimen in 2010, adjusting the doses of isoniazid and pyrazinamide, and adding ethambutol in the intensive treatment phase. Due to the lack of data on serum concentrations of first-line drugs in the brazilian population in this new scheme, this study aimed to determine the serum concentrations of rifampicin, isoniazid and pyrazinamide during treatment and its associations with hematological and biochemical alterations, adverse reactions and clinical outcomes. A prospective cohort study was carried out between september 2013 and november 2016 in two basic health units in the city of Belém (Pará). The most common adverse effects were gastric irritation and pruritus, especially in the intensive phase of treatment and the most frequent clinical outcome was discharge by cure (87.5%). There was a high rate of smear negative (98,90%) in the end of intensive treatment phase. Hematological parameters were determined by automatic cell counter (Cobas 2300®) and biochemical parameters by spectrophotometry (Varian®), which did not present any relevant changes during treatment. The drugs analyzed were rifampicin, isoniazid, and pyrazinamide, and their serum concentrations were determined by reverse phase high performance liquid chromatography (HPLC-RP). Rifampicin and isoniazid presented serum concentrations within the minimum inhibitory concentration (MIC), except for pyrazinamide, which presented values below MIC (3.3 μg/ml), but with a maximum concentration (Cmax) well above the recommended values (63.3 μg/ml). Female patients had higher serum rifampicin concentrations than males. The serum concentrations of rifampicin and isoniazid did not show significant variations between the intensive phase and the maintenance phase. The findings of this study allow us to conclude that the current treatment is safe and effective, since the minor adverse reactions were the most frequent, there were no relevant hematological and biochemical alterations, and the majority of the patients evolved to cure.
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Perfil microbiológico e taxa de letalidade das infecções primárias de corrente sanguínea nas crianças menores de um ano em um hospital público de Belém/Pa.
(Universidade Federal do Pará, 2019-12-19) LOPES, Cássia de Barros; FUZII, Hellen Thais; RODRIGUES, Anderson Raiol
Primary Bloodstream Infections (BSI) are among the most prevalent health care-related infections (HAI) and are associated with high morbidity and mortality, especially in young children, preterm, low birth weight newborns and admitted in intensive care units (ICU) . These infections are even more severe when caused by antimicrobial resistant microorganisms common to clinical practice. To determine the type of etiological agents involved in primary BSI acquired hospitals and to know the local profile of antibiotic resistance will improve an appropriate choice of empirical antibiotic therapy and consequent positive impact on clinical outcomes. The objective of this study was to know the microbiological profile and mortality rates of primary BSI in children under one year of age in a public hospital of Belem, a maternal and referral maternity hospital in northern Brazil. A retrospective cohort study was conducted utilizing demographic and microbiologic data and clinical outcome of laboratory-confirmed primary BSIs with a blood culture positive for a known pathogen and its antibiotic susceptibility which was assessed using an automated system Vitek2 (bioMérieux, France), between april 2015 and april 2018. There were 1736 cases of IPCS in children under one year of age with 631 blood culture positive with pathogenic strains. Candida e Klebsiella were the three most prevalent genders; premature newborns, males and low birth weight were the most affected. The ESBL phenotype (extended-spectrum beta-lactamase / extended-spectrum beta-lactamase) occurred in 70,8% Serratia marsecens. Overall crude mortality was elevated, 36,3% (224/617). Use of central venous catheter, mechanical ventilation and admitted in UCI were risk factors to mortality. In multivariate analysis, the pathogen Candida (p = 0.05) was the most significantly associated with deaths. Hospital IPCS are serious adverse events and are associated with a high fatality rate in children under one year of age.
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Perfil epidemiológico, letalidade e caracterização molecular de Pseudomonas aeruginosa multirresistentes, produtoras de metalobetalactamases de isolados clínicos em Unidade de Terapia Intensiva na região Norte
(Universidade Federal do Pará, 2014) MATOS, Eliseth Costa Oliveira de; CARNEIRO, Irna Carla do Rosário Souza; http://lattes.cnpq.br/4389330944043163; LIMA, Karla Valéria Batista; http://lattes.cnpq.br/9795461154139260
The bacterial resistance is responsible for major concerns about the great problems on health systems. The proposal of this study was to determine the epidemiological, lethality and molecular characteristics of Pseudomonas aeruginosa isolated from patients admitted to the Intensive Care Unit (ICU) in a teaching hospital in city of Belem, Pará, Brazil and analyze the performance of susceptibility testing for P. aeruginosa in automated VITEK -2 to study the antimicrobial resistance. The target people of this study consisted of 54 patients with P. aeruginosa infection at the adult , pediatric and neonatal ICUs from January 2010 to March 2012. For the epidemiological research, demographic data, comorbidities, length of stay were collected. Episodes of Healthcare-associated infections were defined in accordance to Center for Disease Control and Prevention (CDC), use of invasive procedures, previous therapy and patient outcome, Jackson MacCabe score, APACHE II score and Charlson score were documented. The bacterial identification was performed by biochemical tests and VITEK-2 system. The sensitivity test was performed with the application of the method of broth microdilution , and detection of metallo-beta-lactamase by the double disc and PCR method. The test of Genotyping was made by amplification throug DiversiLab system. The P. aeruginosa was the second most common pathogen in the hospital and this occurrence was higher in the adult ICU. The respiratory infection was predominant in the adult ICU, while bloodstream infection was prevalent in pediatric and neonatal ICU. The multidrug resistance was higher in the adult ICU, the average age of patients was 28 years, with an average length of stay of 87.1 days, the diseases were potentially fatal and major risk factors for acquisition of PaMR infection were the use of mechanical ventilation and urinary catheterization. Through the meta-analysis study, we found that infections caused by MR strains showed higher mortality rate, and were twice as likely to death occurs, multidrug resistance a factor of poor prognosis in patients with infection PaMR. Four isolates producers blaSPM-1 variant was detected and genotyping figured the presence of genetic similarity greater than 97%, the changes observed may be related to selective pressure existing in the adult ICU, coupled with inadequate therapy. This study demonstrated the importance of investigations of infections with multidrug-resistant pathogens in critical care units, contributing to these data the possibility of better monitoring and control of these infections.
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Análise da ação do tratamento de mobilização neural em pacientes com neuropatia hansênica
(Universidade Federal do Pará, 2014) CABRAL, André dos Santos; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
Historically Leprosy is one of the most disabling diseases in the world. The symptoms of the disease shows a resultant infectious mixed peripheral neuropathy of an insidious inflammatory process involving an ecological relationship between Mycobacterium leprae and man. Clinical disease turns around, both positive signs such as pain, paresthesia and dysesthesia; as negative signals such as sensorimotor loss and autonomic disturbances. Clinic is similarly developed in patients affected by peripheral compressive neurological syndromes. The neural mobilization has proven an effective manual therapeutic resource in controlling the symptoms of these compression syndromes. The inflammatory nature of leprosy neuropathy perform a compressive action and limiting of the mobility of peripheral nerve, impacting negatively with part of the pathology of the disease. This work aimed to investigate the neural mobilization technique is able to improve the symptoms of leprosy neuropathy. Therefore developed a clinical study, longitudinal, non-randomized, self-control, with an experimental analysis of quantitative character, consisting of four different moments, evaluation, experimental intervention period and revaluation 1 and 2. Were examined 12 upper limbs of six patients with high poliquimioterapêutico scheme for multibacillary for clinical form Borderline, who had neurological neurological impairment and remaining neural symptoms. A total of 23 nerve trunks still were symptomatic during the evaluation, taking an average of 3.8 ± 1.8 per patient nerve trunks. Most incidents symptoms to palpation assessment were paresthesia (20) and pain (09). The average intensity of neuropathic pain of each MS was 6.33±3.24. It still has measured grip strength and the sensitivity of the palm side for comparison after the intervention. After 12 sessions of neural mobilization upper limbs there was a slight improvement of sensitivity and grip strength but it was not significant. At the end of the experimental treatment, the number of symptomatic nerve trunks of upper limb decreased significantly. It was also observed analgesia of all upper limbs treated, with maintenance of this benefit after a post-expiration month of the intervention period. With these results we can conclude that the treatment of neural mobilization proved to be effective in controlling leprosy neuropathic pain.
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Estado nutricional e desenvolvimento motor de crianças ribeirinhas expostas ao mercúrio no estado do Pará - Amazônia brasileira
(Universidade Federal do Pará, 2014-11-26) LIMA, Antônio César Matias de; PINHEIRO, Maria da Conceição Nascimento; http://lattes.cnpq.br/6353829454533268
Several studies have shown that riverside children from Amazon are exposed to mercury at levels that can be harm to the development. Although, no previous study evaluated the consequences of exposure to the neurodevelopment of this population. The methods used did not take into account the different interfering factors in the child development. We aim to assess the children's motor development and its relation to mercury exposure, nutritional status and socioeconomic profile of the families of local children in two different geographic regions of Pará, Tapajós river basin (São Luiz do Tapajós and Barreiras communities) and Tocantins river basin (Furo do Maracujá community). The demographic and socioeconomic information of families were obtained through the ABEP socioeconomic questionnaire, 2012. For the analysis of anthropometric measurements the WHO AnthroPlus v 1.0.2 software was used (for children above 5 years). Hair sample were used to quantify the total Hg analysis by atomic absorption spectrophotometry. To analyze the children development was used the Test of Gross Motor Development - Second Edition (TGMD-2) Ulrich (2000). The mercury exposure levels of children in the Tapajos were significantly higher than the children from Tocantins. In all schoolchildren groups the social status were categorized as very poor. Children from São Luiz do Tapajós had higher frequency of underweight and stunting than the other children population. In the overall assessment, Barreiras community showed better performance in manipulative skills, locomotor and gross motor coefficient than the others. There was no difference between the children of São Luiz do Tapajós and Furo do Maracujá that had the worst performers. There was no difference between the children from São Luiz do Tapajós and Furo Maracujá. The correlation between the total Hg and motor development markers was observed in Barreiras, while between body mass index and developing markers were observed in the Furo do Maracujá and Barreiras. These results suggest the influence of mercury on the motor development of school, alone and in association with nutritional factors. The TGMD2 is a viable technique in the evaluation of riparian school engine development and may be recommended for other groups of children with similar socioeconomic conditions for this study.
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Estudo do perfil de pacientes submetidos a pesquisa de Helicobacter pylori: análise endoscópica e dos fatores determinantes da atividade linfocitária na resposta imunológica gástrica (ROR-Y, FOXP3 e GATA3)
(Universidade Federal do Pará, 2015) MIRANDA, Ariney Costa de; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
INTRODUCTION: Helicobacter pylori is known for its adaptability to the host may progress to chronic infection using diverse and effective mechanisms of pathogenicity. It has high worldwide incidence and its direct relationship with peptic ulcer, gastritis, gastric carcinoma and lymphoma occurs in a minority of infected individuals. A better understanding of the genetic regulation of gastric immune response, motivated this investigation. OBJECTIVES: Describe the transcription factors of T lymphocytes positive for ROR-γ, FOXP3 and GATA3, correlating them with the intensity, type and degree of activity of gastritis, caused by H. pylori infection METHODS: The study included 50 patients of both sexes who underwent upper gastrointestinal endoscopy with biopsy. Urease test and histology were made for identification and confirmation of infection by the bacteria. Thirty-five samples were sent to the immunopathology laboratory NMT-UFPA to study gene expression of transcription factors of T lymphocytes (ROR- γ, FOXP3 and GATA3) by RT-PCR method. RESULTS: We obtained 48.5% positive H. pylori urease test in patients and 25.7% positive of H. pylori in the histological study. The confirmation of H. pylori held by these two exams was 11.7%. In this sample, 22% of individuals reported having a previous Helicobacter pylori infection. The age and gender of the individuals did not influence the gene expression of the studied factors. The H. pylori positive individuals showed a higher expression of the GATA3 gene with prior infection report, and mild erosive gastritis body classified by the Sydney system via endoscopy. The ROR-γ gene presented with increased expression only when comparing samples with or without positive for H. pylori (histology), by the topography of the inflammatory process evidenced by endoscopy. The terms of the factors in the study were more significant when we used the β-actin gene as standard when compared to the GAPDH gene. CONCLUSIONS: The adult age group analyzed in our sample did not influence the gene expression of the studied transcription factors. 2- There were not found differences in the genes expressions that were studied, related to gender of the sample. 3- There was a significant gene expression not only in the patients that were H. pylori positive (histology), but also in the ones who reported previous infection in our study. 4-To compare the endoscopic findings of the sample using the Sydney system with the gene expression of transcription factors under study, we obtained better agreement only in the degree of activity of gastritis. 5- The transcription factor GATA3 (TH2 response profile) was the highest gene expression in samples with endoscopic gastritis and tested positive for H. pylori. 6- The transcription factor ROR-γ (TH17 response profile) presented with increased expression when comparing samples with the topography of the inflammatory process evidenced by endoscopy, regardless of positive H. pylori (histology). 7- The gene β-actin gene as a constituent standard used in our study was that showed significant results in quantified terms, when compared to the GAPDH gene.
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Estimativa da não adesão ao tratamento da malária em área endêmica no Marajó estado do Pará
(Universidade Federal do Pará, 2014) ALMEIDA, Eduardo Dias; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
The association of Chloroquine (CQ) and Primaquine (PQ) is used as first-line treatment for malaria caused by Plasmodium vivax in Brazil. Treatment failure of this association is recognized worldwide and frequently reported. Multifactorial, involving related to the host, the vector and the etiological agent variables. Among these, treatment adherence is critical to establish the efficacy and effectiveness of antimalarial drugs, because the behavior of non-compliance tends to increase the rates of parasite recurrence and foster the emergence of strains resistant to antimalarial drugs. Despite the high incidence of P. vivax malaria in the Brazilian Amazon basin, few studies have evaluated treatment adherence and behavioral factors and environmental determinants. This study aimed to estimate the rate of non-adherence to treatment of P. vivax malaria in the municipality of Anajás, PA. We conducted a survey of demographic data (age, location, gender) and observational studies on the perception of the local population about the disease and its treatment. Then become a validated instrument to measure non-adherence to treatment in different metrics, based on the study by Morisky et al. (1986), with the addition of an item on the self-replication of doses for use in patients with P. vivax malaria. Finally, we proposed an evaluation model of non-adherence based on therapeutic drug monitoring of pharmacokinetic parameters of CQ, considering different scenarios of noncompliance. The results showed that the disease occurs in both sexes and in most cases are from rural areas. Risk factors such as gender, origin, parasitaemia at admission to treatment and age had no significant impact on rates of nonadherence. However, the abandonment of treatment to feel better, the need to return to work, or worse activities, the adverse effects of CQ, were the key behaviors for non-compliance to full treatment regimen. The instrument for measuring non-adherence, consisting of five items presented satisfactory validation parameters, in particular in its Likert scale dichotomized so that estimated non-adherence to the therapeutic regimen in 33.3%. After construction and validation of the mono-compartmental pharmacokinetic model by non-linear regression and evaluation of various scenarios for non-adherence, it is found that the loss of two consecutive doses without replacement was regarded as the only scenario that can significantly change the pharmacokinetic parameters and CK interfere with the therapeutic response.
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“Citomegalovírus: diversidade genética e pesquisa de resistência antiviral em pacientes imunodeficientes da cidade de Belém”
(Universidade Federal do Pará, 2015-07-17) SILVA, Dorotéa de Fátima Lobato da; SOUSA, Rita Catarina Medeiros; http://lattes.cnpq.br/3560941703812539
Cytomegalovirus (CMV) is one of the most common cause of morbidity and mortality in immunocompromised patients because its latency and reactivation mechanism that commonly occurs in immunodeficiencies. Genetic analysis showed that the virulence of the strains may be related to genotypic diversity. The main objective of this paper was to describe the seroepidemiology profile and genetic diversity of CMV by detecting mutations that confer viral resistance to ganciclovir in immunodeficient patients from Belém city.A total of 671 samples were analyzed: 243 HIV/AIDS, 257 neoplastic patients, 112 kidney transplant and 60 people with SLE. The seroprevalence of antibodies was 96.1% and active infection and levels of 2.4% (n = 16) lower than that observed by qPCR method which corresponded to 15.63%. Differences in infection rates due to low sensitivity (5.71%) of the serological method demonstrated in screening test. The mutation research was made in 82 samples for pyrosequencing method, a 741pb segment of the UL97 gene was amplified, between 1087-1828 nucleotides. It was observed that 100% (n = 82) of samples had two mutations in amino acid in codon 596 (E596K) and another one in codon 604 (S604F). The S604F mutation was not found in other viral sequences from GenBank. Ten other mutations occurred between codons 377 and 594 in eight samples, including the A594V mutation in a renal transplant patient who ended up dying.It was concluded that the prevalence of antibodies and the epidemiological profile of the group were similar to those observed in populations of developing countries; the viral infection rates are related to viral reactivation, being underestimated by serology; sequence analysis revealed significant genetic diversity in the samples examined; detection of A594V mutation suggests circulating strains with resistance mutation.
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Epidemiologia molecular das infecções por adenovírus em crianças com gastrenterite aguda grave, após a introdução da vacina contra rotavírus na cidade de Belém, Pará
(Universidade Federal do Pará, 2017-02-10) MÜLLER, Elza Caroline Alves; LINHARES, Alexandre da Costa; http://lattes.cnpq.br/3316632173870389; SOUSA, Maisa Silva de; http://lattes.cnpq.br/1775363180781218
Gastroenteritis are the third cause of infant morbidity and mortality worldwide, especially among children under 5 years old. Adenoviruses (HAdV) are icosahedral non-enveloped viruses, possess 240 proteins "hexon" specific and a double-stranded DNA. They belong to the Adenoviridae family, Mastadenovirus genus, and are assigned to 7 species (A to G) and 57 serotypes. Epidemiological studies found that HAdVs account for 2-14% of cases of acute childhood diarrhea in hospitals and outpatient units. The aim of this study was to determine the prevalence and to assess the epidemiological features of of HAdV infection, as well as the occurrence of types in 842 children under three years of age, hospitalized for acute gastroenteritis in Belém, Brazil. All of these children had been vaccinated against rotavirus.These children were selected from a previous rotavirus vaccine case-control study conducted at Instituto Evandro Chagas, Belém, Pará, from May 2009 to April 2011. ELISA and immunochromatography were used for HAdV screening in stool samples and PCR and oligonucleotide sequencing for typing and molecular characterisation. HAdVs were found in 7.2% (61/842) of the tested samples, with the enteric adenoviruses (EAD) accounting for 50.8% (31/61) of the HAdV positive cases. The distribution of HAdV according to the gender showed that 7.7% (28/362) of whom were female and 6.8% (33/480) were male. The highest prevalence rates of HAdV infection were seen among patients older than 24 months of age, corresponding to 8.9% (16/178) of all positive cases. In regards to the temporal distribution, the highest prevalence rate was observed in June, representing 11.4% (8/70) of cases overall. The oligonucleotide sequencing showed that HAdV species F was predominant in our region, accounting for 64.5% (29/45) of the sequenced samples. These samples included HAdV types 41 and 40, detected at rates of 69% (20/29) cases and 31% (9/29), respectively. The results of this study indicate that HAdV accounts for a significant proportion of gastroenteritis among hospitalized children aged less than 3 years, during a post-rotavirus vaccine introduction period in Belém, Pará state, Brazil.
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Dor neuropática crônica hansenica: serie de casos clínicos com ênfase no diagnóstico e terapêutica com toxina botulínica tipo A
(Universidade Federal do Pará, 2014) SOUSA, Emanuel de Jesus Soares de; XAVIER, Marília Brasil; http://lattes.cnpq.br/0548879430701901
Neuropathic pain is a chronic pain syndrome is difficult to treat often affects patients with leprosy. Treatment advocates the use of analgesic, anti-inflammatory hormone or not, codeine, tricyclic antidepressants, neuroleptics, anticonvulsants and thalidomide, but without uniforms, and fully satisfactory results. OBJECTIVE: To describe patients with chronic neuropathic pain leprosy, clinical forms, damaged nerves, motor and sensory syndromes, clinical diagnosis, Electrodiagnostic, and evaluation of the WHOQOL - Bref, with emphasis on the treatment of chronic neuropathic pain using botulinum toxin type A (TxBA). METHODOLOGY: 15 patients with chronic neuropathic pain. We used specific protocol including clinical, demographic, DN4 protocol, analog scale (VAS), sensory evaluation, and motor electromyography and evaluation of the WHOQOL- Bref. Performed therapeutic intervention with botulinum toxin type A 100U BOTOX® administered subcutaneously. Patients were evaluated on days 0, 10 and 60, the WHOQOL - Bref was performed on days 0 and 60. RESULTS: The scores ranged from DN4 - 5 and 9, Analogue Scale VAS pain between 5 and 10, all patients experienced sensory changes, motor and electromyography in 01 cases there was complete pain relief in 60 days, others showed improvement in the first week with the return of symptoms with less intensity after this period, the WHOQOL - Bref comparing the moments before and after treatment with TxBA, all areas had an increase in QOL scale, areas with significant quality of life and physical. CONCLUSION: The patients had continuous, persistent refractory to standard treatment neuropathic pain of high intensity. Using TxBA proved to be a good therapeutic option in relieving the painful condition, with improved quality of life for these patients.
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Padrão de resposta imunológica periférica em pacientes infectados pelo HTLV-1 e sua correlação com as manifestações neurológicas funcionais nos indivíduos com PET/MAH
(Universidade Federal do Pará, 2014) DIAS, George Alberto da Silva; FUZII, Hellen Thais; http://lattes.cnpq.br/0026958665547973
Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the central nervous system (CNS); however, the mechanism by which HTLV-1 induces HAM/TSP is not yet clear. The virus–host interaction may provoke changes in the immunological response, such as the enhanced production of inflammatory cytokines, which are implicated in the pathogenesis of HAM/TSP. This work aimed to analyze the peripheral immune response of patients infected with HTLV-1 and correlate it with functional neurological manifestations in patients with HAM/TSP. In the current study, 69 HTLV-1 infected patients were studied. 26 of them developed HAM/TSP and 43 didn’t develop HAM/TSP. In patients with HAM/TSP was evaluated the functional neurological manifestations like muscle strength, muscle tone, balance and walking aid. Five mL peripheral blood was collected into a tube with EDTA and lymphomononuclear cells were separated on a Ficoll-PaqueTM Plus density gradient (GE Healthcare). Total RNA was extracted from 106 cells with Trizol reagent. After RNA quantification, 1 μg of total RNA was submitted to reverse transcription for the generation of cDNA using the Superscript III kit (Invitrogen). IFN-, TNF-, IL-4, IL-10 and TGF- gene expression was measured quantitatively with the StepOnePlus Real-Time PCR System (Applied Biosystem) using SYBR Green reagent (Applied Biosystem). The amount of mRNA in the sample was expressed as the relative amount to the GAPDH and β-actin genes, according to the formula 2-Ct, where Ct is Ctgene – Cthousekeeping gene. The gene expression showed higher expression of Th1 cytokine in patients with and without HAM/TSP, principally IFN-. In HAM/TSP patients also showed higher TNF- expression. The gene expression showed lower expression of Th2 cytokine in patients with HAM/TSP. As regards the anti-inflammatory response, gene expression of IL-10 showed impaired in patients with HAM/TSP and expression of TGF- initially showed higher in both groups. After ratio analysis between TGF-andIL it was observed that the expression of TGF-wasequivalent to the expression of IL-10, suggesting its involvement as a non-inflammatory cytokine, but as possible repair action tissue. The inflammatory profile was positively associated with the walking aid and balance, showing significant results only for the expression of IFN-. The patients infected with HTLV-1 who developed HAM/TSP showed increased Th1 response compared to patients who did not develop HAM/TSP, and this increased expression of IFN- is related to the development and progression of the disease.
Acesso aberto (Open Access)
Análise de série temporal da hanseníase no estado do Pará
(Universidade Federal do Pará, 2016) PINHEIRO, Helder Henrique Costa; ARAÚJO, Marizeli Viana de Aragão; http://lattes.cnpq.br/7849256617873180; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
Objective: Analysing a time series of new cases detected of Leprosy in the State of Pará, checking epidemiological trends according to the observated variables of the disease. Methods: Ecological observational design of detection historical series of Leprosy cases with use of secondary data from the National Notifiable Diseases System. The detection rates and the general variables in studies and estimated the trends of the time series were calculated. The State of Pará data were compared to the States of Mato Grosso State and Rio Grande do Sul. Results: The detection rate in Pará in 2014 was 4,84 per 10.000 inhabitants, with 32.177 cases detected in the period 2008-2014, estimating a trend annual growth rate of -12.71%. The proportion of children under 15 years of age was 10.4%, the largest in Brazil. Higher frequency of MB cases (65,2%) and Borderline clinical form (45,2%) was deteceted. Conclusion: The detection of new cases of leprosy is mainly in adult men, poorly educated and living in urban areas. The downward trend in case detection of the disease is different from stationary trend in the State of Mato Grosso. However, the trend of leprosy cases in children and adolescents in the State of Pará is stationary.
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A influência dos polimorfismos nos genes interferons lambda 3 lambda 4 e ancestralidade genética na infecção crônica pelo vírus da hepatite c e na resposta ao tratamento em uma população miscigenada de Belém-Pará-Brasil
(Universidade Federal do Pará, 2015) AMARAL, Ivanete do Socorro Abraçado; SANTOS, Eduardo José Melo dos; http://lattes.cnpq.br/6647221517242357; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
Chronic infection by Hepatitis C virus is a global public health problem in which more than half of infected people evolves to chronicity and can progress to cirrhosis with its complications as well as hepatocellular carcinoma. This study aimed to describe the polymorphisms in genes IL-28B and IFNL4 in a population of Belém with chronic infection by hepatitis C because they can influence the therapeutic response and the natural history of this infection. Three hundred and sixty-six patients were attended at Santa Casa de Misericórdia do Pará Hospital, confirmed by RT-PCR and 243 controls. The SNPs studied were determined by PCR Real Time technique and ancestry was assessed using 48 INDEL markers validated for European, African and Indian parental populations. Contributions of African, European and Amerindian ancestry were found in patients and controls, respectively (0.06 vs 0.04), (0,58 vs 0.662) (0.275) vs (0.214). The frequencies of rs-860 C/C, C/T, T/T (C/T and T/T) in patients and controls were respectively: (21% vs 38%), 59% vs 48%), (19% vs 14%), (79% vs 62%). The rs-917 genotype frequencies in patients and controls showed no significance and genotype frequencies in ss-590 were similar to those in rs-860. As predictors of therapeutic response: female gender, age below 45 years old, hepatic fibrosis stage (F1F2), rs-917 genotype T/T, HCV RNA <600.000UI/ml and platelets levels ≥ 150 x104 / mm3. Therapeutic response was associated with the rs-917 T/T and its mutant allele in heterozygous or homozygous was associated with therapeutic failure and F3 F4. In conclusion, from the point of view of genetics, one nitrogenous base exchange on a particular chromosome leads to large repercussions on different studied populations interfering with aspects related to the response to therapy, natural course of HCV infection. This information could lead to individualized treatment with better prospects of responses, increased vigilance for certain patients more likely to progress to more advanced stages of fibrosis and hepatocellular carcinoma.
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Avaliação epidemiológica, clínica e molecular de enteropatógenos causadores de diarreia aguda em crianças e adultos residentes na comunidade Quilombola do Abacatal, Ananindeua, Pará
(Universidade Federal do Pará, 2015) KAIANO, Jane Haruko Lima; MASCARENHAS, Joana D'Arc Pereira; http://lattes.cnpq.br/5156164089432435
Acute diarrheal disease is a major cause of morbidity and mortality in developing countries and one of the factors that contributes to the worsening of the nutritional status of children. This study aimed to evaluate the clinical, epidemiological and molecular profile of infections by viral and parasitic agents in children aged 0-10 years and those over 10 years of quilombo of Abacatal in the 2008-2010 period. Fecal samples from 294 children were collected in the age group 0-10 years and 81 individuals over 10 years, residents of the community Abacatal, Ananindeua, Pará, which had acute diarrhea board or without diarrhea (controls). The viral diagnosis was made by immunochromatographic and molecular tests and parasitological by Faust and Hoffman method. A total of 375 fecal samples were obtained from 177 individuals. The frequency of viral agents in this study were rotavirus group A rotavirus C and picobirnavirus group by 6.4% (24/375), 0.3% (1/375) and 1.3% (5/375 ), respectively.The polyacrylamide gel electrophoresis confirmed the presence of rotavirus in 23 of 10 samples (43.48%) having short profile of 13 (56.5%) long profile. The presence of intestinal parasites was observed in 272 (77.94%) samples, and the most common were Ascaris lumbricoides detected in 13.18% (46/349) of the samples, followed by Trichuris trichiura with 10.88% (38 / 349), hookworms with 4.01% (14/349) and Strongyloides stercoralis 1.72% (6/349). Of the 24 samples positive for rotavirus group A the following genotypes were detected: G2P [4] (12.50%, 3/24); G1P [8] (25.00%, 6/24), G3P [9] (29.20%, 7/24) and G12P [6] (33.33%, 8/24). Two new genotypes were detected for VP6 genes (I18) and NSP1 (A19) of rotavirus A. Nutritional assessment of 38 children was conducted, showing that 18 4% (7/38) presented malnourished. This study highlights the need to implement preventive actions in the community, including education measures for health, vaccination against rotavirus, and even the implementation of programs to control parasitic infestations.
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Avaliação do dano neural periférico sensitivo e motor em pacientes hansenianos, com HIV/AIDS e co-infectados Hanseníase/HIV utilizando-se a avaliação neurológica simplificada e técnicas complementares
(Universidade Federal do Pará, 2015) ACÁCIO, José Augusto Bastos; XAVIER, Marília Brasil; http://lattes.cnpq.br/0548879430701901
According to the Ministry of Health, in 2014 Brazil had 24,612 new cases of leprosy. The number of individuals living with HIV increased by 11% in Brazil between 2005 and 2013. Leprosy and HIV infection are two chronic infectious diseases that have important geographical overlap in our country. Therefore, co-infection of these two diseases, it became also important in terms of public health. However, recent studies have shown that the overlap of these two conditions does not alter the clinical course (immunological or histological) thereof, and that the incidence of leprosy is not increased in HIV-infected patients. Mycobacterium leprae shows no increase in prevalence in co-infection with HIV, as well as the generalized immunosuppression of AIDS does not affect the manner of presentation of leprosy. This study aims to evaluate the peripheral nerve damage in leprosy patients with HIV / AIDS and co-infected with leprosy / HIV using the evaluation protocol of the Ministry of Health and an additional assessment to check for possible interference related factors will infection HIV neurological evaluation of the co-infected patient leprosy / HIV. It was developed through an analytical cross-sectional study comparing three groups: (1) 20 patients with leprosy; (2) 20 patients with HIV / AIDS and (3) with 18 patients with co-infection leprosy / HIV. The simplified neurological assessment when used in the HIV virus carriers group and of patients with co-infection leprosy / HIV could not identify, when present, nerve damage from the HIV infection or the use of ART in the groups in question, it does not investigate important neuromuscular disorders and characteristics of peripheral neuropathies affecting the patient with HIV / AIDS, but not carrier of leprosy. Evaluation complement the present study was important to detect important changes that could go unnoticed among the three groups. Especially for people with HIV where there doesn’t seem to be a guide that guides the neurological assessment regarding the impairment of the peripheral nervous system in this group. What would enable early detection and subsequent treatment that would enable preventive measures or treatment for the frame found, thus preventing the possible worsening and the installation of after-effects that might reasonably interfere with the welfare bio-psycho-social that individual.
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Caracterização fenotípica das moléculas de adesão endotelial e leucocitária em amostras de lesão cutânea na doença de Hansen
(Universidade Federal do Pará, 2015) SOUZA, Juarez de; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
Introduction: The infection caused by Mycobacterium leprae leads to a complex relationship parasite-host relationship based mainly on immunopathological aspects, that may result in lepromatous form, preseting a Th2 cell profile, or in the tuberculoid pole presenting a Th1 immune pattern. Rationale: In this process it was necessary to analyze the participation of the endothelium through expression profile of adhesion molecules, thus trying to understand how cell migration occurs in leprosy. Main Objective: the study will determine the profile of expression of adhesion molecule and the participation of the endothelium in the selection of cells to the formation of the inflammatory infiltrate seen in the disease. Specific objectives: to quantify the expression of the adhesion molecules ICAM-1; ICAM-2, VCAM-1; VLA-4; E-selectin; P-selectin. To analyze the expression of adhesion molecules according to the standard histopathological type infiltrate the poles of the disease. Quantitatively evaluate the presence of adhesion molecules and correlate these adhesins with different cell patterns seen at the poles of the infection. Methodology: The skin samples were sectioned taken portions were subjected to immunohistochemical analysis using monoclonal antibodies to ICAM-1; ICAM-2; VCAM-1; VLA-4; P-selectin and E-selectin markers. Results: immunostaining of ICAM-1, VCAM-1 and VLA-4 adhesins, showed a greater presence of these molecules on the endothelium of the tuberculoid form (TT) of the infection. ICAM-1 was presented with 9.92±1.11 cells/mm2 on TT form, whereas LT pole showed 5.87±1.1 cells/mm 2. The VCAM-1 averaged 18.28±1.46 cells/mm2 in TT form, while the lepromatous had on average 10.67±1.25 cells/mm2. The analysis of E-Selectin showed that the infection tuberculoid is present in an amount (13.00±1:59 cells/mm2), significantly (p <0.0001) higher than E-selectin when compared to lepromatous pole which had only 2.58±0:38 cells/mm2. Discussion: The increase quantity of immunoglobulins ICAM-1 and VCAM-1 result in strengthening the signaling of transmigration tissue through the relationship between LFA-1 with its endothelial connector ICAM-1. This same mechanism is involved in strengthening the relationship between the endothelium and migration of cells with Th1 profile towards the tissue. VLA-4 is directly linked to the infiltration of Th1 cell lines, being the mediator of the increased frequency of T CD4+ cells in inflamed tissue. The lack of VLA-4 and of VCAM-1 immunoglobulin can also result in inhibition of adhesion of Th1 lymphocytes. It is also important to notice that the ICAM-1 and VCAM-1 deficiency influences the migration of T CD8+ lymphocytes thus altering the presence of cytotoxic cells in the tissue. Conclusion: The study strengthens the role of the endothelium as one responsible for the profile found in tissue cells. Correlating the expression of adhesion molecules to the selectivity in cell migration, resulting in a direct influence on the immune response present in leprosy.