Resumo em Inglês:

Abstract Resistance to benznidazole in certain strains of Trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. This work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of T. cruzi epimastigote forms (Y, Bolivia, SI1, SI8, QMII, and SIGR3). The last four strains have been recently isolated from triatominae and mammalian host (domestic cat). The expression of mitochondrial tryparedoxin peroxidase was analyzed by the Western blotting technique using polyclonal antibody anti mitochondrial tryparedoxin peroxidase obtained from a rabbit immunized with the mitochondrial tryparedoxin peroxidase recombinant protein. All the tested ferrocenyl diamine hydrochlorides were more cytotoxic than benznidazole. The expression of the 25.5 kDa polypeptide of mitochondrial tryparedoxin peroxidase did not increase in strains that were more resistant to the ferrocenyl compounds (SI8 and SIGR3). In addition, a 58 kDa polypeptide was also recognized in all strains. Ferrocenyl diamine hydrochlorides showed trypanocidal activity and the expression of 25.5 kDa mitochondrial tryparedoxin peroxidase is not necessarily increased in some T. cruzi strains. Most likely, other mechanisms, in addition to the over expression of this antioxidative enzyme, should be involved in the escape of parasites from cytotoxic oxidant agents.

Resumo em Inglês:

Abstract Introduction Despite the high prevalence of chronic pain in individuals infected with HTLV-1, predictive and protective factors for its development are still unclear. Objective To identify factors associated with chronic pain in individuals with HTLV-1. Methods This cross-sectional study was conducted in a reference center for treatment of patients infected with HTLV-1 in Salvador, Bahia, Brazil. The study included individuals infected with HTLV-1, over 18 years, and excluded those with difficulty to respond the pain protocol. Data on sociodemographic, health behavior, and clinical characteristics were collected in a standardized way. The prevalence ratio (PR) of pain is described, as well as the factors independently associated with the presence of pain, which were assessed by multiple logistic regression. Results A total of 142 individuals were included in the study, mostly female (62.7%), aged 20–64 years (73.2%), married (61.3%), with less than eight years of education (54.2%), and with a steady income (79.6%). Multivariate analysis showed that being symptomatic for HTLV-1 – sensory manifestations, erectile dysfunction, overactive bladder, and/or HAM/TSP (PR = 1.21, 95% CI: 1.05 to 1.38), self-medication (PR = 1.29, 95% CI: 1.08–1.53), physiotherapy (PR = 1.15, 95% CI: 1.02–1.28), and depression (PR = 1.14, 95% CI: 1.01–1.29) were associated with an increased likelihood of presenting pain. On the other hand, physical activity (PR = 0.79, 95% CI: 0.67–0.93) and religious practice (PR = 0.83, 95% CI: 0.72–0.95) were associated with a decreased likelihood of having pain. Conclusion The use of self-medication, physiotherapy and the presence of depression are independently associated with neurological symptoms in HTLV-1 infected patients. Religious practice and physical activity are both protective for the development of pain.

Resumo em Inglês:

Abstract Introduction: Latin America is a large and diverse region, comprising more than 600 million inhabitants and one million physicians in over 20 countries. Resistance to antibacterial drugs is particularly important in the region. This paper describes the design, implementation and results of an international bi-lingual (Spanish and Portuguese) online continuing interprofessional interactive educational program on hospital-acquired infections and antimicrobial resistance for Latin America, supported by the American Society for Microbiology. Methods: Participation, satisfaction and knowledge gain (through pre and post tests) were used. Moreover, commitment to change statements were requested from participants at the end of the course and three months later. Results: There were 1169 participants from 19 Latin American countries who registered: 57% were physicians and 43% were other health care professionals. Of those, 1126 participated in the course, 46% received a certificate of completion and 54% a certificate of participation. There was a significant increase in knowledge between before and after the course. Of 535 participants who took both tests, the grade increased from 59 to 81%. Commitments to change were aligned with course objectives. Discussion: Implementation of this educational program showed the feasibility of a continent-wide interprofessional massive course on hospital acquired-infections in Latin America, in the two main languages spoken in the region. Next steps included a new edition of this course and a "New Challenges" course on hospital-acquired infections, which were successfully implemented in the second semester of 2015 by the same institutions.

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Abstract Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS – 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS ≥ 2″, when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years. Time trends of resistance were analyzed by Cochran–Armitage test. We observed a decrease in the rate resistance mutations for PI, NRTI, "IAS – 3 class mutations", and "No fully susceptible drugs" over these 11 years, from 69.2% to 20.7%, 92.3% to 90.2%, 46.2% to 22.5%, and 12.8% to 5.7%, respectively (p < 0.05). Resistance to NNRTI increased from 74.4% to 81.6%, mainly because of K103N mutation. The GSS score ≥2 increased during the years from 35.9% to 87.3% (p < 0.001). We demonstrate that resistance to PI and to the three main classes simultaneously are declining, although the number of patients on of antiretroviral therapy has doubled in the last ten years in Brazil (125,000 in 2002 to 400,000 in 2014). Broader resistance testing and the availability of more therapeutic options might have influenced this decline. The increase in NNRTI resistance can limit this class as first line treatment in Brazil in the future.

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Abstract Objective: Maintaining a right balance between Th17 and Treg might be critical to the immunopathogenesis of active tuberculosis (TB). This study aimed to assess whether the Th17/Treg balance is altered in active TB patients. Methods: 250 study subjects (90 active TB patients, 80 latent TB subjects, and 80 healthy controls) were recruited for the study. The expression of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) in the 250 subjects was investigated by flow cytometry. Plasma levels of cytokines IL-17 and IL-10, which are related to Th17 and Treg, respectively, were determined by ELISA. Results: The percentages of Th17 and Treg in PBMCs from active TB patients were significantly higher than those from latent TB or control groups (Th17: 4.31 ± 1.35% vs. 1.58 ± 0.71% or 1.15 ± 0.49%, p < 0.05; Treg: 11.44 ± 2.69% vs. 7.54 ± 1.56% or 4.10 ± 0.99%, p < 0.05). The expression of IL-17 and IL-10 was significantly increased in active TB patients in comparison to that in latent TB or control groups (IL-17: 16.85 ± 9.68 vs. 7.23 ± 5.19 or 8.21 ± 5.51 pg/mL, p < 0.05; IL-10: 28.70 ± 11.27 vs. 20.25 ± 8.57 or 13.94 ± 9.00 pg/mL, p < 0.05). Conclusions: Our study demonstrated an altered balance of Treg/Th17 in active TB patients, with higher percentages of Th17 and Treg in PBMCs. Further research on this imbalance may offer a new direction for TB treatment.

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Abstract Background: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. Methods: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. Results: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15–19 (OR = 2.86; 95% CI: 2.09–3.91) and 20–39 years old (OR = 2.30; 95% CI: 1.81–2.92) were more likely to default on TB treatment than those aged 0–14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR = 2.22; 95% CI: 1.43–3.44) or other causes (OR = 2.86; 95% CI: 2.14–3.83). Black patients were more likely to default on TB treatment (OR = 1.33; 95% CI: 1.22–1.44) and die from TB (OR = 1.50; 95% CI: 1.29–1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR = 1.94; 95% CI: 1.73–2.17), death due to TB (OR = 1.46; 95% CI: 1.25–1.71), death due to other causes (OR = 1.38; 95% CI: 1.21–1.57) and MDR-TB (OR = 2.29; 95% CI: 1.46–3.58). Conclusions: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

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Abstract The purpose of this study was to identify the risk factors that predispose patients who are hospitalized with pressure ulcers (PUs) colonized by Gram-negative bacilli (GNB) to develop bacteremia. In addition, we also detected main phenotypes of resistance in infected and uninfected PUs. A prospective cohort study was conducted at the Clinical Hospital of the Federal University of Uberlândia including patients with Stage II or greater PUs, colonized or not with GNB, from August 2009 to July 2010. Infected ulcers were defined based on clinical signs and on positive evaluation of smears of wound material translated by a ratio of polymorphonuclear cells to epithelial cells ≥2:1, after Giemsa staining. A total of 60 patients with Stage II PUs were included. Of these 83.3% had PUs colonized and/or infected. The frequency of polymicrobial colonization was 74%. Enterobacteriaceae and GNB non-fermenting bacteria were the most frequent isolates of PUs with 44.0% of multiresistant isolates. Among patients who had infected PUs, six developed bacteremia by the same microorganism with a 100% mortality rate. In addition, PUs in hospitalized patients were major reservoir of multiresistant GNB, also a high-risk population for the development of bacteremia with high mortality rates.

Resumo em Inglês:

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.

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Abstract Chagas disease reactivation has been a defining condition for acquired immune deficiency syndrome in Brazil for individuals coinfected with Trypanosoma cruzi and HIV since 2004. Although the first coinfection case was reported in the 1980s, its prevalence has not been firmly established. In order to know coinfection prevalence, a cross-sectional study of 200 HIV patients was performed between January and July 2013 in the city of Pelotas, in southern Rio Grande do Sul, an endemic area for Chagas disease. Ten subjects were found positive for T. cruzi infection by chemiluminescence microparticle immunoassay and indirect immunofluorescence. The survey showed 5% coinfection prevalence among HIV patients (95% CI: 2.0–8.0), which was 3.8 times as high as that estimated by the Ministry of Health of Brazil. Six individuals had a viral load higher than 100,000 copies per µL, a statistically significant difference for T. cruzi presence. These findings highlight the importance of screening HIV patients from Chagas disease endemic areas.

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Abstract Staphylococcus aureus is an important cause of bloodstream infections. Therefore, the main purpose of this work was to characterize a collection of 139 S. aureus isolates from bloodstream infections in two public hospitals in relation to their antimicrobial susceptibility profile, staphylococcal cassette chromosome mec types, and clonal relationship. Methicillin resistance and resistance to other 12 agents were accessed by the disk diffusion test. Minimum inhibitory concentration to mupirocin was also determined. The SCCmec types were accessed by multiplex PCR, and the clonal relationship was determined by pulsed field gel electrophoresis method and restriction modification system characterization. Besides, multilocus sequence typing was performed for representative methicillin-resistant S. aureus isolates. The military hospital showed a dissemination of the New York/Japan (USA100/ST5/CC5/SCCmecII) lineage associated to multidrug resistance, including mupirocin resistance, and the teaching hospital presented polyclonal and non-multidrug resistant MRSA isolates. Complete substitution of the Brazilian endemic clone by other lineages was found in both hospitals. These findings can highlight differences in policy control and prevention of infections used in the hospitals and a change in the epidemiological profile of MRSA in Brazilian hospitals, with the replacement of BEC, a previously well-established clone, by other lineages.

Resumo em Inglês:

Abstract In this study, we evaluated trends in hospitalization rates, length of stay and in-hospital mortality in a cohort of HIV-infected patients in Rio de Janeiro, Brazil, from 2007 through 2013. Among the 3991 included patients, 1861 hospitalizations occurred (hospitalization rate of 10.44/100 person-years, 95% confidence interval 9.98–10.93/100 person-years). Hospitalization rates decreased annually (per year incidence rate ratio 0.92, 95% confidence interval 0.89–0.95) as well as length of stay (median of 15 days in 2007 vs. 11 days in 2013, p-value for trend < 0.001), and in-hospital mortality (13.4% in 2007 to 8.1% in 2013, p-value for trend = 0.053). Our results show that, in a middle-income setting, hospitalization rates are decreasing over time and non-AIDS hospitalizations are currently more frequent than those related to AIDS. Notwithstanding, compared with high-income settings, our patients had longer length of stay and higher in-hospital mortality. Further studies addressing these outcomes are needed to provide information that may guide protocols and interventions to further reduce health-care costs and in-hospital mortality.

Resumo em Inglês:

Abstract Here we report the case of a patient who developed urinary tract infection after a urodynamic study. The causative agent was Raoultella planticola, a rare opportunistic pathogen that usually invades immunocompromised patients. While a urinary tract infection with R. planticola has been previously described, this is the first report in which an R. planticola infection developed after a urodynamic study. We postulate that the mechanism of infection was direct invasion of the urinary tract from contaminated urodynamic study equipment. Here, we discuss the role played by isotonic solutions in facilitating bacterial reproduction.