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Abstract This article reviews tuberculosis control actions performed over the last decade, at a global level. The perspectives for the fulfillment of the goals of the new Global Tuberculosis Elimination Plan are described, where the insertion of social protection (Pillar 2) and research (Pillar 3) will play an innovative and strategic role, especially in high-burden countries, like Brazil.

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Abstract Actinomycosis remains characteristically uncommon, but is still an important cause of morbidity. Its clinical presentation is usually indolent and chronic as slow growing masses that can evolve into fistulae, and for that reason are frequently underdiagnosed. Actinomyces spp is often disregarded clinically and is classified as a colonizing microorganism. In this review of literature, we concomitantly present 11 cases of actinomycosis with different localizations, diagnosed at a tertiary hospital between 2009 and 2016. We outline the findings of at least one factor of immunosuppression in > 90% of the reported cases.

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Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

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Abstract INTRODUCTION The functioning of the immune system during pregnancy is altered in both human immunodeficiency virus (HIV)-infected and uninfected women. Unfavorable socioeconomic conditions have been indicative of higher morbidity and mortality and worsening of the immune system. The aim of this study was to correlate social status with levels of interleukin (IL)-10 (non-inflammatory) and interferon-gamma (IFN-γ; inflammatory) cytokines. METHODS A cross-sectional study was conducted with three groups of women: 33 pregnant HIV-infected (G1); 40 non-pregnant, HIV-infected (G2); and 35 pregnant, HIV-uninfected. To measure the social status, a compound indicator called the social status index (SSI), was established using sociodemographic variables (i.e., education level, housing conditions, per capita income, and habitation and sanitary conditions). RESULTS The HIV-infected women had a higher proportion of unfavorable SSI (73% and 75% of G1 and G2, respectively). There were significantly lower IL-10 levels in the G1 group with both unfavorable and favorable SSI than in the other groups. No significant difference in IFN-γ levels was observed among groups. However, the G1 group had higher IFN-γ values among both favorable and unfavorable SSI groups. CONCLUSIONS Higher rates of unfavorable conditions, including lower education levels, IL-10 levels, and a trend for higher IFN-γ levels, were identified among HIV-infected women, pregnant and non-pregnant. These factors may interfere in health care and lead to poor outcomes during pregnancy. Therefore, we suggest that health policies could be created to specifically address these factors in this population.

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Abstract INTRODUCTION Infections caused by respiratory viruses are important problems worldwide, especially in children. Human metapneumovirus (hMPV) is a respiratory pathogen and causes severe infections with nonspecific symptoms. This study reports the hMPV occurrence and dissemination in southern Brazil and compares the frequency of occurrence of this virus and the human respiratory syncytial virus (hRSV) in the epidemiological weeks in a three-year period (2009-2011). METHODS: In total, 545 nasopharyngeal (NP) specimens from individuals with Severe Acute Respiratory Syndrome (SARS) who were negative for other seven respiratory viruses were analyzed for the presence of hMPV. Human metapneumovirus was detected by direct immunofluorescence and real-time reverse transcription polymerase chain reaction. RESULTS: hMPV was detected in 109 patients from the main geographic regions of the southernmost state of Brazil, presenting similar overall prevalence in males (46.8%) and females (53.2%). Among children who were less than six years old, hMPV was detected in 99 samples of all age groups, with a higher frequency in infants who were less than one year old (45.7%) compared to all other age groups until six years. hMPV and hRSV infection occurred in almost the same epidemiological weeks (EWs) of each year, with peaks of incidence between EW 31/37 and EW 26/38 for the years 2009 and 2011, respectively. hMPV was further detected in several cases of SARS and it was the only virus detected in three deaths. CONCLUSIONS These findings indicate that hMPV is in circulation in southern Brazil and highlight the importance of diagnosing hMPV for influenza-like illness in the population.

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Abstract INTRODUCTION: Rabies is an acute zoonotic disease, caused by a rhabdovirus that can affect all mammals, and is commonly transmitted by the bite of a rabid animal. The definitive diagnosis is laboratorial, by the Fluorescent Antibody Test (FAT) as a quick test and Mouse Inoculation Test (MIT) as a confirmatory test (gold standard). Studies conducted over the past three decades indicate that MIT and Virus Isolation in Cell Culture (VICC) can provide the same effectiveness, the latter being considered superior in bioethics and animal welfare. The aim of this study was to compare VICC with MIT, in terms of accuracy, biosafety and occupational health, supply and equipment costs, bioethics and animal welfare, in a Brazilian public health lab. METHODS: We utilized 400 samples of animal neurological tissue to compare the performance of VICC against MIT. The variables analyzed were accuracy, biosafety and occupational health, time spent in performing the tests, supply and equipment costs, bioethics and animal welfare evaluation. RESULTS: Both VICC and MIT had almost the same accuracy (99.8%), although VICC presented fewer risks regarding biosafety and mental health of the technicians, and reduced time between inoculation and obtaining the results (approximately 22 days less). In addition, VICC presented lower supply costs (86.5% less), equipment costs (32.6% less), and the advantage of not using animals. CONCLUSIONS: These results confirm that VICC can replace MIT, offering the same accuracy and better features regarding cost, results, biosafety and occupational health, and bioethics and animal welfare.

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Abstract INTRODUCTION: Multidrug-resistant (MDR) Escherichia coli, a species that is a leading cause of urinary tract infections (UTIs) and is a major global public health concern. This study was designed to detect the differences in antibiotic resistance patterns, the production and type of extended spectrum β-lactamases (ESBLs), and the clonal relationships among E. coli isolates from UTIs and fecal samples. METHODS: Antibacterial resistance was determined by the disk diffusion method. ESBL, carbapenemase, and AmpC-producing isolates were detected phenotypically. Then, the ESBL genes were sequenced to detect the type. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) was performed on the ESBL-positive isolates. RESULTS: The most common effective antibacterial agents were colistin, imipenem, and amikacin. Among the isolates, 204 (56.6%) were MDR. Of the 163 ESBL-positive isolates, 11 (6.7%) produced AmpC, and the frequencies of beta-lactamase-positive genes were as follows: bla CTX-Mgroup1, 76%; bla TEM1, 74.8%; bla SHV12, 1.2%; and bla OXA1, 12.88%. ERIC PCR showed a diverse pattern, suggesting that clonal spread of E. coli in this area is uncommon, and that most of the infecting strains are endogenous. CONCLUSIONS: The high rates of antibacterial-resistant and MDR isolates are quite important since these strains can act as source of resistant bacteria that can be spread in the community. Controlling antibiotic use, against inappropriate use and abuse, in the community and continuous surveillance of emerging resistance traits are critical to controlling the spread of resistance.

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Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

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Abstract INTRODUCTION: Knowledge of the epidemiological profile and risk factors for Toxoplasma gondii infection among postpartum women is a relevant issue, because this protozoan can be vertically transmitted to the developing fetus, which can cause severe and debilitating disease. The aim of this study was to assess the risk factors associated with T. gondii infection in postpartum women in Goiânia, GO, Brazil. METHODS: This cross-sectional study comprised 229 postpartum women, among whom 204 were chronically infected (IgG+/IgM-), and 25 were seronegative (IgG-/IgM-; control group). All the patients were asked to complete a form to provide sociodemographic, clinical, dietary, and cultural information. The data were analyzed to compare seropositivity and risk factors based on the odds ratio (OR) thereof. RESULTS: The sociodemographic characteristics associated with the risk for toxoplasmosis were: education ≤ 8 years [OR: 2.521, confidence interval (CI): 1.01-6.301, p=0.049], and age ≥ 30 years (OR: 4.090; CI: 1.180-14.112, p=0.023). Clinical and behavioral characteristics related to eating raw and undercooked meat, were not found to be risk factors associated with a positive test for toxoplasmosis. CONCLUSIONS: Our findings concur with the results of other studies conducted in Brazil and abroad, where variables such as low levels of schooling, and advanced age (≥ 30 years) are major risk factors for pregnant women to become infected with T. gondii.

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Abstract INTRODUCTION: Chikungunya virus (CHIKV) can negatively influence outcomes in patients with pre-existing conditions. We investigated the association between the recent CHIKV outbreak and increased type 2 diabetes (T2D)-attributable deaths. METHODS: Monthly averages of T2D-attributable deaths between 2001 and 2016 were determined and compared to the equivalent data for 2017 and the recent CHIKV outbreak. RESULTS: CHKV outbreak peaked in April 2017 with 4,394.4 cases/100,000 inhabitants, while T2D-attributable deaths in the same period increased by 35.2%. CONCLUSIONS: T2D-attributable deaths significantly increased compared to the previous data, which overlapped with CHIKV incidence. The pathophysiology of this association warrants further investigations.

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Abstract INTRODUCTION: Pseudo-infectious yellow fever viral particles (YFV-PIVs) have been used to study vaccines and viral packaging. Here, we report the development of a packaging cell line, which expresses the YFV prM/E proteins. METHODS: HEK293 cells were transfected with YFV prM/E and C (84 nt) genes to generate HEK293-YFV-PrM/E-opt. The cells were evaluated for their ability to express the heterologous proteins and to package the replicon repYFV-17D-LucIRES, generating YFV-PIVs. RESULTS: The expression of prM/E proteins was confirmed, and the cell line trans-packaged the replicon for recovery of a reporter for the YFV-PIVs. CONCLUSIONS: HEK293-YFV-prM/E-opt trans-packaging capacity demonstrates its possible biotechnology application.

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Abstract INTRODUCTION: the Building Infestation Index (BII) uses the Rapid Assay of the Larval Index for Aedes aegypti (LIRAa) to express the relationship between positive and surveyed properties. We evaluated LIRAa and the relationship between the BII and climate variables for dengue cases in Foz do Iguaçu municipality, Paraná. METHODS: Spearman’s correlations for mean precipitation, mean temperature, BII, and dengue cases (time lag). RESULTS: positive correlations between BII and cases, and mean temperature and cases at two months. Weak correlation between precipitation and cases at three months. CONCLUSIONS: LIRAa and climate variables correlate with dengue cases.

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Abstract INTRODUCTION The occurrence of Triatoma sordida in the Brazilian Western Amazon is reported for the first time. METHODS Triatoma sordida specimens were collected from a Gallus gallus nest in a peridomiciliary area of Senador Guiomard municipality in the state of Acre. RESULTS The number of triatomine species in Acre increased from six to seven with this first report of T. sordida in the Brazilian Western Amazon. CONCLUSIONS The occurrence of T. sordida in Acre is of concern since it is among the most captured triatomines in peridomiciliary environments in Brazil, and carries a high potential for vector transmission.

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Abstract INTRODUCTION: Hymenoptera injuries are commonly caused by stinging insects. In Amazonas state, Brazil, there is no information regarding distribution, profile, and systemic manifestations associated with Hymenoptera injuries. METHODS: This study aimed to identify risk factors for systemic manifestation using the Brazilian Notifiable Diseases Surveillance System (2007 to 2015). RESULTS: Half of Hymenoptera injuries were caused by bee stings. Hymenoptera injuries were concentrated in Manaus, and 13.36% of cases displayed systemic signs. Delayed medical assistance (4 to 12 hours) presented four times more risk for systemic manifestations. CONCLUSIONS: Simple clinical observations and history of injury are critical information for prognostic improvement.

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Abstract INTRODUCTION. This study aimed to evaluate different methods for differentiation of species of coagulase-negative staphylococci (CoNS) that caused infections in hospitalized immunocompromised patients. METHODS. A total of 134 CoNS strains were characterized using four different methods. RESULTS. The results of matrix assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) analysis were in complete agreement with those of tuf gene sequencing (kappa index = 1.00). The kappa index of Vitek 2® Compact analysis was 0.85 (very good) and that of the conventional method was 0.63 (moderate). CONCLUSIONS . MALDI-TOF MS provided rapid and accurate results for the identification of CoNS (134; 100%).

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Abstract INTRODUCTION: Here, we determined the genes encoding antibiotic resistance enzymes and virulence factors and evaluated the genetic relationship between Enterobacter spp. isolated from different clinical samples. METHODS: A total of 57 clinical isolates of Enterobacter spp. were tested for the production of extended-spectrum β-lactamases (ESBLs), carbapenemase, and AmpC using phenotypic and genotypic methods. RESULTS: The most common ESBLs and AmpC β-lactamases were bla TEM (63.3%) and bla EBC (57.7%), respectively. The most prevalent virulence gene was rpos (87.7%). The random amplified polymorphic DNA (RAPD) patterns of strains were genetically unrelated. CONCLUSIONS: RAPD polymerase chain reaction analysis revealed high genetic diversity among isolates.

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Abstract INTRODUCTION: Bacille Calmette-Guérin (BCG) downmodulates allergen-specific IgE levels and prevents other atopic responses in experimental models but fails to protect against respiratory allergies. Human responsiveness to BCG is variable and may interfere with protection. METHODS: Multivariate models were evaluated to test the possible effect of responsiveness (assessed by IFN-γ production) to BCG revaccination on the modulation of total and allergen-specific serum IgE levels in healthy volunteers participating in a randomized controlled trial. RESULTS: Serum total or Derp-specific IgE levels did not change regardless of the increase in IFN-γ levels. CONCLUSIONS: BCG responsiveness does not affect protection against atopy.

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Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden’s factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

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Abstract Visceral leishmaniasis is common in Brazil and is caused by Leishmania (Leishmania) infantum/chagasi. Post-kala-azar dermal leishmaniasis frequently follows visceral leishmaniasis caused by L. donovani, and para-kala-azar dermal leishmaniasis refers to an uncommon presentation wherein it occurs simultaneously along with visceral leishmaniasis. While post-kala-azar dermal leishmaniasis only occurs occasionally in L. infantum/chagasi infections, it frequently occurs in patients with concomitant immunosuppression (HIV co-infection). Here, we describe the first case of para-kala-azar dermal leishmaniasis in Brazil. It is important to raise awareness of post- and para-kala-azar dermal leishmaniasis in L. infantum endemic areas as these patients may contribute to visceral leishmaniasis transmission.

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Abstract Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.

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Abstract The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process. Together with P. lutzii, P. brasiliensis appears to be involved in severe cases of PCM.

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Abstract The most frequent jellyfish in Southern Brazil causes mainly local pain and skin plaques. A 3-year-old female bather presented an erythematous, irregular plaque on the left forearm after contact with a jellyfish and intense facial angioedema with facial flushing. The lungs had vesicular murmur, wheezes, and snorts, and pink and spumous secretion in the airways with intercostal retraction. She was administered subcutaneous adrenaline (0.1mg/kg) and hydrocortisone intravenous (10mg/kg) with total recovery in a few minutes. The manifestations of anaphylactic reactions are distinct from those of envenomations, and prompt and adequate care is fundamental in these situations.