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ABSTRACT Introduction: Use of antibiotic and bacterial resistance is the result of a complex interaction not completely understood. Objectives: To evaluate the impact of entire antimicrobial use (community plus hospitals) on the incidence of bloodstream infections in intensive care units adjusted by socioeconomic factors, quality of healthcare, and access to the healthcare system. Design: Ecologic study using a hierarchical spatial model. Setting: Data obtained from 309 hospitals located in the state of São Paulo, Brazil from 2008 to 2011. Participants: Intensive care units located at participant hospitals. Outcome: Hospital acquired bloodstream infection caused by MDRO in ICU patients was our primary outcome and data were retrieved from São Paulo Health State Department. Socioeconomic and healthcare indexes data were obtained from IBGE (Brazilian Foundation in charge of national decennial census) and SEADE (São Paulo Planning and Development Department). Information on antimicrobial sales were obtained from IMS Brazil. We divided antibiotics into four different groups (1-4). Results: We observed a direct association between the use of group 1 of antibiotics and the incidences of bloodstream infections caused by MRSA (1.12; 1.04-1.20), and CR-Acinetobacter sp. (1.19; 1.10-1.29). Groups 2 and 4 were directly associated to VRE (1.72; 1.13-2.39 and 2.22; 1.62-2.98, respectively). Group 2 was inversely associated to MRSA (0.87; 0.78-0.96) and CR-Acinetobacter sp. (0.79; 0.62-0.97). Group 3 was inversely associated to Pseudomonas aeruginosa (0.69; 0.45-0.98), MRSA (0.85; 0.72-0.97) and VRE (0.48; 0.21-0.84). No association was observed for third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli. Conclusions: The association between entire antibiotic use and resistance in ICU was poor and not consistent for all combinations of antimicrobial groups and pathogens even after adjusted by socioeconomic indexes. Selective pressure exerted at the community level seemed not to affect the incidences of MDRO infection observed in intensive care setting.

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ABSTRACT Background: Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil. Methods: This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year. Results: A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis. Conclusion: Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

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ABSTRACT Background: Tropical spastic paraparesis or HTLV-associated myelopathy (TSP/HAM) may prevent, limit or restrict the performance of daily living activities, and as a consequence, several aspects of life are affected. Objective: The aim of this study was to evaluate activity limitations, risk awareness, social participation, quality of life, and pain in individuals infected with HTLV-1. Methods: This was an observational, descriptive, analytical, cross-sectional study with a quantitative approach. An interview questionnaire, the Screening of Activity Limitation and Safety Awareness (SALSA) scale, the Participation scale, a quality of life questionnaire (SF-36) and the Brief Pain Inventory were used. Results: A total of 55 patients with HTLV-1 were interviewed (62% asymptomatic and 38% symptomatic). In both groups, there was a higher frequency of patients aged 41-50 years old (35.3% asymptomatic and 38.1% symptomatic), with complete secondary education (47.1% asymptomatic and 42.9% symptomatic), and married (64.7% asymptomatic and 52.4% symptomatic). Of the symptomatic patients, 33.3% were retired; among asymptomatic patients, 20.6% performed domestic activities. The majority of patients in both groups had not received blood transfusions. Sexual intercourse was still practiced by patients. After assessment, asymptomatic patients had no activity limitations (64.7%), and symptomatic patients presented limitations (90.5%). None of the groups showed good risk awareness. There was no restriction on social participation in 97.1% of asymptomatic patients and in 52.4% among symptomatics. Both groups complained of pain, being more frequent in the lumbar spine in asymptomatic patients and in the knees in symptomatic patients. Pain was more severe in symptomatic patients and affected aspects of quality of life. Conclusion: The clinical follow-up instruments must be adopted by healthcare professionals to monitor new symptoms so as to avoid the onset of limitations identified in symptomatic patients, in addition to enabling continuous surveillance of asymptomatic patients.

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ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women.

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ABSTRACT Toxoplasmosis in pregnant women can cause significant morbidity and mortality in the fetus, which may be mitigated by early diagnosis and treatment. Social factors have also been related to the risk of developing the congenital form of toxoplasmosis, since some of these factors interfere directly in the quality of prenatal care. This study aimed to describe the clinical, laboratory, and epidemiological data of pregnant women diagnosed with toxoplasmosis and their newborns followed up at a referral hospital in Rio de Janeiro, Brazil. This was descriptive cohort study of 334 pregnant women with toxoplasmosis followed from May 2014 to December 2017. We conducted interviews to assess knowledge about the disease and its preventive measures, analyzed clinical and laboratory data during antenatal visits, and collected data from the newborns' medical charts. Results: This was a predominantly low-income women cohort study, with little schooling, mainly referred from public health services late in pregnancy (178; 53.3%), in the second and third trimesters (286; 85.6%). Diagnosis of acute toxoplasmosis had not been confirmed in 171 cases (51.2%). Out of 183 (54.9%) women who had initiated treatment at the original health services, 45 (24.6%) received an incorrect prescription. Seventy-two amniocenteses were performed, with positive real-time polymerase chain reaction (qPCR) in the amniotic fluid in two cases (2.8%). Congenital toxoplasmosis at birth was identified in eight newborns (5.4%). Conclusion: Late referral to specialized medical services, inadequate toxoplasmosis management at the original prenatal care services, and social vulnerabilities are contributing factors to the persistent occurrence of congenital toxoplasmosis cases.

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ABSTRACT Background: COVID-19 is a new disease and the most common complication is pneumonia. The Radiological Society of North America (RSNA) proposed an expert consensus for imaging classification for COVID-19 pneumonia. Objective: To evaluate sensitivity, specificity, accuracy, and reproducibility of chest CT standards in the beginning of the Brazilian COVID-19 outbreak. Methods: Cross-sectional study performed from March 1st to April 14th, 2020. Patients with suspected COVID-19 pneumonia submitted to RT-PCR test and chest computed tomography (CT) were included. Two thoracic radiologists blinded for RT-PCR and clinical and laboratory results classified every patient scan according to the RSNA expert consensus. A third thoracic radiologist also evaluated in case of discordance, and consensus was reached among the three radiologists. A typical appearance was considered a positive chest CT for COVID-19 pneumonia. Sensitivity, specificity, positive and negative predictive values were calculated. Cohen's kappa coefficient was used to evaluate intra- and inter-rater agreements. Results: A total of 159 patients were included (mean age 57.9 ± 18.0 years; 88 [55.3%] males): 86 (54.1%) COVID-19 and 73 (45.9%) non-COVID-19 patients. Eighty (50.3%) patients had a positive CT for COVID-19 pneumonia. Sensitivity and specificity of typical appearance were 88.3% (95%CI, 79.9-93.5) and 94.5% (95%CI, 86.7-97.8), respectively. Intra- and inter-rater agreement were assessed (Cohen's kappa = 0.924, P = 0.06; Cohen's kappa=0.772, P = 0.05, respectively). Conclusion: Chest CT categorical classification of COVID-19 findings is reproducible and demonstrates high level of agreement with clinical and RT-PCR diagnosis of COVID-19. In RT-PCR scarcity scenarios or in equivocal cases, it may be useful for attending physicians in the evaluation of suspected COVID-19 pneumonia patients attended at the emergency unit.

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ABSTRACT Objective: Staphylococcus aureus infections remain associated with considerable morbidity and mortality in both hospitals and the community. There is little information regarding the role of ovarian hormones in infections caused by S. aureus. The aim of this study was to evaluate the effects of ovariectomy in the immune response induced by S. aureus. Methods: Female mice BALB/c were ovariectomized (OVX) to significantly reduce the level of ovarian hormones. We also used sham-operated animals. The mice were inoculated intraperitoneally with S. aureus. Blood samples were collected for leukocyte count and bacterial quantification. The uterus and spleen were removed and weighed to calculate the uterine and splenic indexes. Lungs were removed and fractionated for immunohistochemical analysis for macrophage detection (anti-CD68) and relative gene expression of IL-6, IL-1β and TNF-α by RT-PCR. Results: Ovariectomy enlarged spleen size and generally increased circulating lymphocytes. OVX females experienced a continuation of the initial reduction of lymphocytes and a monocyte and neutrophil late response compared to shams (p ≥ 0.05). Moreover, OVX females showed neutropenia after 168 h of infection (p ≥ 0.05). Macrophage response in the lungs were less pronounced in OVX females in the initial hours of infection (p ≥ 0.01). OVX females showed a higher relative gene expression of IL-1β, IL-6 and TNF-α in the lung at the beginning of the infection compared to sham females (p ≥ 0.01). Among the uninfected females, the OVX control females showed a higher expression of IL-6 in the lung compared to the sham control females (p ≥ 0.05). In this model, the lack of ovarian hormones caused a minor increase in circulating leukocytes during the initial stage of infection by S. aureus and increased pulmonary gene expression of IL-1β, IL-6, and TNF-α. Ovariectomy alone enlarged the spleen and increased circulating lymphocytes. Ovarian hormones acted as immunoprotectors against S. aureus infection.

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ABSTRACT Background: Helicobacter pylori harbouring cag-pathogenicity island (cagPAI) which encodes type IV secretion system (T4SS) and cagA virulence gene are involved in inflammation of the gastric mucosa. We examined all the 27 cagPAI genes in 88 H. pylori isolates from patients of different ethnicities and examined the association of the intactness of cagPAI region with histopathological scores of the gastric mucosa. Results: 96.6% (n = 85) of H. pylori isolates were cagPAI-positive with 22.4% (19/85) having an intact cagPAI, whereas 77.6% (66/85) had a partial/rearranged cagPAI. The frequency of cag2 and cag14 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominantly found in Chinese isolates. The cag24 was significantly found in higher proportions in Malay and Indian isolates than in Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI with higher density of bacteria and neutrophil activity, whereas strains lacking cagPAI were associated with higher inflammatory score. Conclusions: The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients' ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.

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ABSTRACT Sepsis is one of the most common reasons for hospitalization. This condition is characterized by systemic inflammatory response to infection. International definition of sepsis mainly points out a multi-organ dysfunction caused by a deregulated host response to infection. An uncontrolled inflammatory response, often referred to as "cytokine storm", leads to an increase in oxidative stress as a result of the inhibition of cellular antioxidant systems. Oxidative stress, as well as pro-inflammatory cytokines, initiate vascular endothelial dysfunction and, in consequence, impair microcirculation. Microcirculation damage leads to adaptive modifications of cell metabolism. Moreover, mitochondrial dysfunction takes place which results in increased apoptosis and organ damage. Non-coding RNA fragments, especially miRNA molecules, may play an important role in the pathomechanism of sepsis. Numerous studies have indicated altered expression of various miRNAs in sepsis. miRNAs can be used as markers in the diagnosis and prognosis of disease development. In turn, intracellular miRNAs regulate the TLR4/NFκB pathway responsible for the expression of pro-inflammatory cytokine genes involved in the inflammatory response in sepsis. The understanding of detailed molecular mechanisms leading to organ damage can contribute to the development of specific therapy methods thereby improving the prognosis of patients with sepsis.

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ABSTRACT During SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) pandemic, the etiologic agent of COVID-19, several studies described the involvement of other tissues besides the respiratory tract, such as the gastrointestinal tract. Angiotensin-converting enzyme-2, the functional virus host cell receptor expressed by organs and tissues, seems to have an important role in the pathophysiology and presentation of this disease. In pancreas, this receptor is expressed in both exocrine glands and islets, being a potential target for the virus and subsequent pancreatic injury. There are few articles reporting pancreatic injury in COVID-19 patients but most of them do not report acute pancreatitis. Diagnosing acute pancreatitis secondary to SARS-CoV-2 infection is challenging due to the need to rule out other etiologies as well the notable heterogeneous presentations. Herein we report the case of a patient with COVID-19 who developed severe acute pancreatitis.

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ABSTRACT COVID-19 has raised worldwide concern as spiraling into a pandemic. Reports about comprehensive investigation of COVID-19 viremia are extremely scanty. Herein, we present four COVID-19 patients with positive SARS-CoV-2 nucleic acid test in blood, accounting for 12.12% of 33 detected cases. Rapid deterioration of these cases with septic shock, accompanying with lung CT images enlarged rapidly, decrease of blood oxygen, heart rate drop (with asynchrony of hypoxemia) accompanied with SARS-CoV-2 viremia. It indicates that massive replication and releasing into blood of SARS-CoV-2 and secondary inflammation storm may lead to injury of multiple organs and poor prognosis. So, positive COVID-19 nucleic acid test in blood may be a good forecasting marker of rapid deterioration of COVID-19 pneumonia. In addition, clearance of viremia may indicate tendency for recovery.

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ABSTRACT As of August 30, 2020, Brazil ranked second among countries with the highest number of COVID-19 cases, with the city of São Paulo as the national epidemic epicenter. Local public healthcare institutions were challenged to respond to a fast-growing hospital demand, reengineering care provision to optimize clinical outcomes and minimize intra-hospital coronavirus infection. In this paper we describe how the largest public hospital complex in Latin America faced this unprecedented burden, managing severe COVID-19 cases while sustaining specialized care to patients with other conditions. In our strategic plan a 900-bed hospital was exclusively designated for COVID-19 care and continuity of care to those not infected with coronavirus ensured in other inpatient facilities. After 152 days, 4241 patients with severe COVID-19 were hospitalized, 70% of whom have already been discharged, whereas the remaining Institutes of the complex successfully maintained high complexity inpatient and urgent/emergency care to non-COVID-19 patients.

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ABSTRACT Human astrovirus (HAstV) 1-8 and highly divergent HAstVMLB1−3 genotypes have been detected in children both with and without acute gastroenteritis (AGE). One hundred and seventy fecal samples from children (≤5 years old) living in the Amazon region were evaluated for the presence of HAstV1-8, HAstV MLB1−3 and HAstVVA1−3, using an usual RT-PCR protocol and a new protocol with specific primers designed to detect HAstVMLB1−3. HAstVMLB1 and HAstV MLB2, as well as the HAstV3 and 5 genotypes were detected. HAstVMLB1−2 genotype was detected for the first time in Brazil at a frequency of 3.5% (6/170).