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STUDY OBJECTIVES: The detection of Mycobacterium sp on a culture remains the 'gold standard' technique for the diagnosis of mycobacterial infections. A small percentage of these cultures, however, may be contaminated by other nonfastidious microorganisms, making accurate diagnosis difficult. We evaluated the use of a polymerase chain reaction (PCR) protocol that was specific for the genus Mycobacterium, and specifically for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare, for the identification of Mycobacterium sp growing on contaminated cultures. DESIGN: This prospective study was designed to identify Mycobacterium sp growing on mycobacterial cultures contaminated with other microorganisms.Samples and patients: Twenty-six samples, taken from 23 patients with probable mycobacterial disease, that resulted in Mycobacterium growth but were contaminated during their processing were evaluated in this study. Clinical data and the clinical status of each patient were used to ascertain the final diagnosis. RESULTS: All samples studied here exhibited Mycobacterium growth on solid media but were contaminated by nonfastidious bacteria, compromising the biochemical identification of the Mycobacterium sp. PCR correctly identified the genus Mycobacterium in all samples. M tuberculosis was identified in 14 samples, and M avium in 10 samples. No amplification of M intracellulare was obtained, and in two samples there was amplification only for the genus Mycobacterium. In the cultures of those patients in whom a mycobacterial infection was evident, PCR identified M avium and M tuberculosis in samples from 6 and 12 patients, respectively. However, PCR identified M avium (two patients) and M tuberculosis (two patients) in the cultures of four patients for whom a mycobacterial disease could not be confirmed by our case definition. Finally, in two samples from one patient only the genus Mycobacterium was amplified by PCR. CONCLUSION: PCR, with its advantages of greater speed and effectiveness than conventional detection methods, was successfully used to identify the Mycobacterium sp growing on contaminated cultures. [ABSTRACT FROM AUTHOR]

The present study aims to characterise the pharmacokinetics of rifampicin (RIF) in tuberculosis (TB) patients with and without HIV co-infection, considering the formation of 25-O-desacetyl-rifampicin (desRIF). It is hypothesised that the metabolite formation, HIV co-infection and drug formulation may further explain the interindividual variation in the exposure to RIF. Pharmacokinetic, clinical, and demographic data from TB patients with (TB-HIV+ group; n = 18) or without HIV (TB-HIV- group; n = 15) who were receiving RIF as part of a four-drug fixed-dose combination (FDC) regimen (RIF, isoniazid, pyrazinamide, and ethambutol) were analysed, along with the published literature data on the relative bioavailability of different formulations. A population pharmacokinetic model, including the formation of desRIF, was developed and compared to a model based solely on the parent drug. HIV co-infection does not alter the plasma exposure to RIF and the desRIF formation does not contribute to the observed variability in the RIF disposition. The relative bioavailability and RIF plasma exposure were significantly lower than previously reported for the standard regimen with FDC tablets. Furthermore, participants weighting less than 50 kg do not reach the same RIF plasma exposure as compared to those weighting >50 kg. In conclusion, as no covariate was identified other than body weight on CL/F and Vd/F, low systemic exposure to RIF is likely to be caused by the low bioavailability of the formulation.

Assessment is an essential component for all educational programs and must check competence acquirement while foster and promote learning. Progress Test (PT) is well recognized to assess cognitive knowledge, clinical reasoning and decision making in the clinical context, offering important information about the individual performance and program quality. It is widely used in Brazilian and international medical schools; however, it still has little role in assessing medical residents in Brazil. We present the experience of a PT pilot implementation in an Infectious Diseases residency program over two years. The first, second and third-year residents did four serial exams with 40 multiple choice questions (item)/each. Preceptors were trained on best practices on item writing. All the items were reviewed by a panel of experts and, after approval, included in the item bank. All participants answered a survey on their perceptions about the experience. The final score was higher for the third-year residents in all exam applications. The level of satisfaction was high among the participants, who mentioned the learning opportunity with the exam and the feedback. PT can improve residents' assessment along the training period and residents' performance should guide review and improvement of the programs., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Tuberculosis (TB) in people living with HIV (PLHIV) is usually paucibacillary and the smear microscopy has limitations and may lead to high proportions of non-confirmed pulmonary tuberculosis (NC-PTB). Despite culture being the reference method, it usually takes 6 to 8 weeks to produce the results. This study aimed to analyze the effect of a rapid molecular test (Xpert) in the confirmatory rate of PTB among PLHIV, from 2010 to 2020, in São Paulo state, Brazil. This is an ecological study with time series analysis of the trend and the NC-PTB rates before and after Xpert implementation in 21 municipalities. The use of Xpert started and gradually increased after 2014, while the rate of NC-PTB in PLHIV decreased over this time, being more significant between late 2015 and mid-2017. The city of Ribeirão Preto stands out for having the highest percentage (75.0%) of Xpert testing among PLHIV and for showing two reductions in the NC-PTB rate. The cities with low Xpert coverage had a slower and smaller decrease in the NC-PTB rate. Despite being available since 2014, a significant proportion of PLHIV suspected of PTB in the state of São Paulo did not have an Xpert ordered by the doctors. The implementation of Xpert reduced the NC-PTB rates with growing effect as the coverage increased in the municipality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Faria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Faculty development in health professions education is still challenging in developing countries like Brazil. Work overload and the lack of financial support hinder faculty members' participation. Ribeirão Preto Medical School founded its Center for Faculty Development in 2016. Since then, an essential skills module (ESMo) on health professions education (HPE) has been offered regularly to faculty members and preceptors of seven undergraduate programs. This case study aims to evaluate the impact of this Essential Skills Module on the educational practices of participants two years after attending the module and the challenges faced during the process., Method: The study used a mixed-method approach with a description of the demographic and professional profile data of the ESMo participants. Immediate post-ESMo perceptions (satisfaction and learning) of the participants were determined with structured instruments. Two years later, a semi-structured interview was conducted and recorded to determine the long-term effects (application of learning and behavior changing as an educator). NVIVO® software was used to store and systematize the thematic discourse analysis with a socio-constructivist theoretical framework interpretation., Results: One hundred forty-six participants were included: 86 (59%) tenured faculty members, 49 (33,5%) clinical preceptors, and 11 (7,5%) invited teachers. Most were female (66%), and 56% had teaching experience shorter than ten years. 52 (69%) out of 75 eligible participants were interviewed. The immediate reaction to participating in the module was quite positive and 80% have already implemented an educational intervention in their daily activities. Discourses thematic analysis showed five emerging themes appearing in different frequencies: Changes in teaching activities (98%); Lack of previous pedagogical training (92.3%); Commitment and enthusiasm towards teaching (46.15%); Overlapping functions inside the institution (34.6%) and Challenges for student assessment (23%)., Conclusion: This first in-depth evaluation of the long-term effects of a faculty development intervention in a Brazilian Health Profession Education school showed that participation positively changed participants' teaching & learning practices. These interventions consistently fostered a community of practice and valued faculty development processes in local and national scenarios., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Untreated HIV infection can lead to profound immunosuppression and increase susceptibility of people living with HIV/AIDS (PLHA) to aspergillosis., Objectives: Reporting the burden and natural history of aspergillosis documented in PLHA admitted in five medical centres in Brazil., Patients and Methods: Clinical, epidemiological and laboratory data were collected in all sequential cases of proven or probable aspergillosis documented in PLHA hospitalised in five medical centres between 2012 and 2020., Results: We enrolled 25 patients ageing between 23 and 58 years (mean = 39) including 11 patients with invasive aspergillosis (IA) and 14 with chronic pulmonary aspergillosis (CPA). The prevalence rate of aspergillosis was 0.1% of 19.616 PLHA. Overall, 72.7% of patients with IA exhibited CD4 < 100 cells/mL and 42.8% of patients with CPA exhibited CD4 count >200 cells/mL. Most patients had a history of tuberculosis, especially those with CPA (85.7%). IA was documented after a mean of 16.5 days of hospitalisation, mainly in critically ill patients exposed to corticosteroids and broad-spectrum antibiotics. In the CPA group, a positive culture (71.4%) and radiological alterations were the most frequent findings supporting their diagnosis. Episodes of IA were mostly documented by tissue biopsies. Crude mortality rates were 72.7% and 42.8% in patients with IA and CPA, respectively., Conclusions: Despite being considered an unusual complication in PLHA (0.1%), IA should be considered in patients with profound immunosuppression and pneumonia refractory to conventional therapy. CPA should be investigated in PLHA with chronic deterioration of pulmonary function and previous diagnosis of tuberculosis., (© 2023 Wiley-VCH GmbH.)

COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diagnosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020‒2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admitted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particularly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive aspergillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19., Methods: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1β, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days., Results: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1β., Conclusion: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19., Trial Registration Numbers: RBR-8jyhxh., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB., Objective: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS)., Methods: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis., Results: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period., Conclusions: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.

Background: Antimicrobial resistance is a growing health problem worldwide. One strategy to face this problem in a reasonable way is training health personnel for the rational use of antimicrobials. There are some difficulties associated with medical staff to receiving training with E-learning education, but there is a lack of studies and insufficient evidence of the effectiveness of this method compared to face-to-face learning. Methods: An educational intervention on antimicrobial resistance (AMR) and antimicrobial prescription practice (APP) was designed and implemented using two approaches: face-to-face and E-learning among physicians of the intensive care unit (ICU) and internal medicine ward (IMW) at Eugenio Espejo Hospital in Quito. Modalities of interventions were compared to propose a strategy of continuous professional development (CPD) for all hospital staff. An interventional study was proposed using a quasi-experimental approach that included 91 physicians, of which 49 belong to the IMW and 42 to the ICU. All of them received training on AMR—half in a face-to-face mode and the other half in an asynchronous E-learning mode. They then all participated on APP training but with switched groups; those who previously participated in the face-to-face experience participated in an E-learning module and vice-versa. We evaluated self-perception about basic knowledge, attitudes and referred practices towards AMR and APP before and after the intervention. A review of medical records was conducted before and after training by checking antimicrobial prescriptions for all patients in the ICU and IMW with bacteremia, urinary tract infection (UTI), pneumonia, and skin and soft tissue infection. The study received IRB clearance, and we used SPSS for statistical analysis. Results: No statistically significant difference was observed between the E-learning and the face-to-face methodology for AMR and APP. Both methodologies improved knowledge, attitudes and referred practices. In the case of E-learning, there was a self-perception of improved attitudes (p < 0.05) and practices (p < 0.001) for both AMR and APP. In face-to-face, there was a perception of improvement only in attitudes (p < 0.001) for APP. In clinical practice, the use of antimicrobials significantly improved in all domains after training, including empirical and targeted treatment of bacteremia and pneumonia (p < 0.001) and targeted treatment of UTI (p < 0.05). For the empirical treatment of pneumonia, the mean number of antibiotics was reduced from 1.87 before to 1.05 after the intervention (p = 0.003), whereas in the targeted management of bacteremia, the number of antibiotics was reduced from 2.19 to 1.53 (p = 0.010). Conclusions: There was no statistically significant difference between the effect of E-learning and face-to-face strategy in terms of teaching AMR and APP. Adequate self-reported attitudes and practices in E-learning exceed those of the face-to-face approach. The empiric and targeted use of antimicrobials improved in all reviewed cases, and we observed an overall decrease in antibiotic use. Satisfaction with training was high for both methods, and participants valued the flexibility and accessibility of E-learning.

Objectives: To evaluate the acquisition of surgical skills by otolaryngology residents and established the minimum number of dissections of a lamb's model to be performed before practicing on human patients., Methods: Nineteen second-year otolaryngology residents performed ten dissections each, five on each nasal cavity, always practicing the same three surgical procedures on the lamb model. Each student's training lasted 2-months, and the entire training intervention lasted 4-years, over four generations of residents. All dissections were recorded and were selected at random for examination by two independent otolaryngology surgeons, who were otherwise not involved in the research. Assessment of the 190 dissections used an instrument validated for surgical training of medical residents., Results: To a 1% significance level, statistical analysis revealed increased performance and satisfactory results were observed after the sixth dissection. Furthermore, after the eighth dissection, skill acquisition was relevant and sustained., Conclusion: Training in endoscopic nasal surgery on a lamb's head model improves surgical skills and handling of surgical instruments. Our results showed the relevance of the lamb model for training in otolaryngology surgery, impacting on patient safety., (Copyright © 2022 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Aims: To investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV-infected Brazilians under treatment with EFV-containing antiretroviral (ART) regimens., Methods: HIV-positive adults (n = 82) on stable ART regimens containing 600 mg EFV once daily for at least 6 months were recruited at 2 university hospitals. Blood samples collected at mid-dose interval were used to quantify the plasma concentrations of EFV (denoted [EFV]), its major metabolite 8-OH-EFV ([8-OH-EFV]) and [8-OH-EFV]/[EFV] metabolic ratio, and to genotype single nucleotide polymorphisms in CYP2B6 (rs3745274, c.516G > T; rs28399499, c.983 T > C) and ABCB1 (rs3842, c.4036G > A). CYP2B6 metabolic phenotypes were inferred from the CYP2B6 diplotypes. Linear regression modelling was applied to identify sociodemographic, clinical and pharmacogenetic predictors of [EFV] and [8-OH-EFV]/[EFV] metabolic ratio., Results: Wide (50-fold) interindividual variation in [EFV], [8-OH-EFV] and [8-OH-EFV]/[EFV] was observed; 69.5% of participants had [EFV] within the nominal therapeutic range (1000-4000 ng/mL), while 19.5 and 11.0% had [EFV] below and above this range, respectively. Multiple regression modelling retained only CYP2B6 metabolic phenotypes or the combined rs3745274 and rs28399499 genotypes, as significant predictors of [EFV] and [8-OH-EFV]/[EFV]., Conclusion: EFV exposure and disposition varied widely among HIV-infected Brazilians under stable treatment with EFV-containing ART regimens. About 1/10 of the participants had [EFV] exceeding nominal supratherapeutic concentration (4000 ng/mL), but reported tolerance to the ARV regimens, while 1/5 of participants had nominal subtherapeutic [EFV] (<1000 ng/mL) but adequate virological response. Genotype for the 2 CYP2B6 single nucleotide polymorphisms studied explained 48% of variation in [EFV] and 35% of variation in [8-OH-EFV]/[EFV]., (© 2022 British Pharmacological Society.)

We correlated clinical, epidemiological, microbiological, and genomic data of an outbreak with polymyxin B (PB)- and carbapenem-resistant Klebsiella pneumoniae during the COVID-19 pandemic. Twenty-six PB- and carbapenem-resistant K. pneumoniae were isolated from patients in the COVID-19 ICU (Intensive Care Unit), non-COVID-19 ICU (Intensive Care Unit), clinical, or surgical ward. Bacterial identification, drug susceptibility tests, and DNA sequencing were performed, followed by in silico resistance genes identification. All isolates showed extensively drug-resistant (XDR) phenotypes. Four different sequence types (ST) were detected: ST16, ST11, ST258, and ST437. Nineteen isolates were responsible for an outbreak in the ICU in September 2020. They belong to ST258 and harbored the 42Kb IncX3plasmid (pKP98M3N42) with the same genomic pattern of two K. pneumoniae identified in 2018. Twenty-four isolates carried bla -KPC-2 gene. No plasmid-mediated colistin ( mcr ) resistance genes were found. Eight isolates presented mgrB gene mutation. The clonal isolates responsible for the outbreak came from patients submitted to pronation, with high mortality rates in one month. XDR- K. pneumoniae detected during the outbreak presented chromosomal resistance to PB and plasmid-acquired carbapenem resistance due to KPC production in most isolates and 42Kb IncX3(pKP98M3N42) plasmid carrying bla KPC-2 was associated with ST258 isolates. The outbreak followed the collapse of the local healthcare system with high mortality rates.

We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.

There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first-line anti-tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB-HIV- group; n = 15) and HIV positive (TB-HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB-HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB-HIV+ patients, dose-normalized plasma exposure area under the curve from zero to 24 h (nAUC 0-24 ; geometric mean and 95% confidence interval [CI]) values at steady-state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74-24.59), 238.21 (95% CI 191.09-296.95), and 18.33 (95% CI 14.56-23.09) µg∙h/ml, respectively. Similar plasma exposure was found in the TB-HIV- patients. The geometric mean and 90% CI of the ratios between TB-HIV- and TB-HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: To identify and synthesize the scientific knowledge produced regarding the effectiveness of the GeneXpert test in the diagnosis of pulmonary tuberculosis (TB) in people living with HIV/AIDS., Methods: Integrative literature review, which was searched on Embase, Scopus, PubMed, Cinahl, Academic Search Premier, Socindex, and LILACS platforms, in December 2019. The studies surveyed went through two stages of selection: reading of titles and abstracts by two reviewers independently; using the Rayyan platform and reading. Nineteen primary studies in English, Portuguese, and Spanish that answered the study's guiding question were included: How effective is the GeneXpert test in the diagnosis of pulmonary TB in people living with HIV/AIDS?, Results: The use of GeneXpert substantially increased the detection of TB cases among the population co-infected with HIV/AIDS, with sensitivity ranging from 68% to 100%, superior to sputum smear microscopy. Specificity ranged from 91.7% to 100%; the positive predictive value from 79.2% to 96.1%; and the negative predictive value from 84.6% to 99.3%. These values were considered similar to sputum smear microscopy by most studies. We also compared these results with different ways of performing culture and other molecular tests, being considered inferior only to the Xpert Ultra., Conclusion: It is possible to affirm that places with a high incidence of HIV/AIDS would benefit from the implementation of the GeneXpert test, entailing effectiveness in diagnosing pulmonary TB in this population when compared to sputum smear microscopy, a widely used test for detection of cases.

Some studies have demonstrated a high prevalence of Candida species in patients with tuberculosis (TB). This is most likely due to long-term antimicrobial therapy. To date, no longitudinal studies addressed the effects of anti-TB treatment on the fungal burden and virulence of Candida spp. This study investigated the prevalence and virulence of Candida spp. in the oral cavity of 30 TB patients at different stages of treatment through a cohort study. These results were compared with those of 60 systemically healthy individuals in a cross-sectional study. Oral rinse samples from TB patients were collected before 45 and after 120 days of treatment. In the control group, the biological samples were collected only once. Candida spp. were identified by restriction fragment length polymorphism (RFLP) assays, and the following virulence factors were studied: phospholipase C and proteinase production, as well as Candida spp. biofilm and hyphae formation. The clinical diagnosis of TB and its treatment time were associated with the greater fungal burden (p < 0.0001), presence of non-albicans Candida (NAC) species (p = 0.0003), and increased virulence factors when compared with the Candida spp. isolated from systemically healthy individuals. The results showed that anti-TB treatment time was responsible for the increased fungal burden and isolation of NAC in TB patients (p = 0.0233). The increased prevalence, quantification, and virulence of Candida spp. isolated from the oral cavity of TB patients highlight the greater risk of oral lesions and cases of systemic dissemination in these patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Antimicrobial resistance has worsened since the onset of COVID-19., Methods: This study involved patients admitted to the adult intensive care unit (ICU) of a tertiary hospital. Pre- and post-COVID-19 data were analyzed. The healthcare-related infections (HCRIs) reported between January 2018 and January 2020 and during the pandemic between February and July 2020 were compared., Results: Antimicrobial resistance increased during the pandemic, especially for Klebsiella pneumoniae isolates, with a rate increase from 5% to 50% for Polymyxin B., Conclusions: The susceptibilities of the main pathogens associated with HCRIs in the ICU changed and should be considered in managing severe COVID-19.

Objective: to identify the prevalence of latent tuberculosis in patients with chronic kidney disease on hemodialysis and associated factors., Method: a cross-sectional study conducted with 176 patients with chronic kidney disease on hemodialysis. The tuberculin test was performed with the standardized antigen, distributed by the Brazilian Ministry of Health, and the reading occurred after 72 to 96 hours of the application. An association test (Chi-square, Fisher's exact), prevalence ratio, and multivariate regression tests were performed., Results: the prevalence of latent tuberculosis diagnosed through Tuberculosis Skin Test was 8.5% (15/176). The "has/has had diabetes" (aOR: 0.117; 95%CI: 0.015-0.92) and "having regular garbage collection (aOR: 0.076; 95%CI: 0.008-0.702) factors were associated with a lower probability of having a Positive skin test., Conclusion: the low prevalence of latent tuberculosis identified and the factors associated with it reinforce the need for screening for latent tuberculosis infection for diabetics combined with an analysis of previous risk factors and comorbidities.

Introduction: This epidemiological household survey aimed to estimate the prevalence of the current and past SARS-CoV-2 infections in Ribeirão Preto, a municipality of southeast Brazil., Methods: The survey was conducted in two phases using a clustered sampling scheme. The first phase spanned May 1-3 and involved 709 participants. The second phase spanned June 11-14, 2020, and involved 646 participants., Results: During the first phase, RT-PCR performed on nasopharyngeal swabs was positive at 0.14%. The serological tests were positive in 1.27% of the patients during the first phase and 2.79% during the second phase. People living in households with more than five members had a prevalence of 10.83% (95%CI: 1.58-74.27) higher than those living alone or with someone other. Considering the proportion of the positive serological test results with sex and age adjustments, approximately 2.37% (95%CI: 1.32-3.42) of the population had been cumulatively infected by mid-June 2020, which is equivalent to 16,670 people (95%CI: 9,267-24,074). Considering that 68 deaths from the disease in the residents of the city had been confirmed as at the date of the second phase of the survey, the infection fatality rate was estimated to be 0.41% (95%CI: 0.28-0.73). Our results suggest that approximately 88% of the cases of SARS-CoV-2 infection at the time of the survey were not reported to the local epidemiological surveillance service., Conclusions: The findings of this study provide in-depth knowledge of the COVID-19 pandemic in Brazil and are helpful for the preventive and decision-making policies of public managers.

To describe the medium-term ophthalmological findings in patients recovering from COVID-19. Patients recovered from the acute phase of COVID-19 underwent a complete ophthalmological evaluation, including presenting and best-corrected visual acuity (BCVA), refractometry, biomicroscopy, tonometry, break-up time and Schirmer tests, indirect ophthalmoscopy, color fundus picture, and retinal architecture evaluation using optical coherence tomography. Socio-demographic data and personal medical history were also collected. According to the severity of systemic manifestations, patients were classified into mild-to-moderate, severe, and critical. Sixty-four patients (128 eyes) were evaluated 82 ± 36.4 days after the onset of COVID's symptoms. The mean ± SD duration of hospitalization was 15.0 ± 10.7 days. Seven patients (10.9%) had mild-to-moderate, 33 (51.5%) severe, and 24 (37.5%) critical disease. Median [interquartile ranges (IQR)] presenting visual acuity was 0.1 (0-0.2) and BCVA 0 (0-0.1). Anterior segment biomicroscopy was unremarkable, except for dry eye disease, verified in 10.9% of them. The mean ± SD intraocular pressure (IOP) in critical group (14.16 ± 1.88 mmHg) was significantly higher than in severe group (12.51 ± 2.40 mmHg), both in the right (p 0.02) and left eyes (p 0.038). Among all, 15.6% had diabetic retinopathy, and two patients presented with discrete white-yellowish dots in the posterior pole, leading to hyporreflective changes at retinal pigment epithelium level, outer segment, and ellipsoid layers. The present study identified higher IOP among critical cases, when compared to severe cases, and discrete outer retina changes 80 days after COVID-19 infection. No sign of uveitis was found.

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

The aim of the study was to compare the impact of 12-week resistance training with blood flow restriction (G RTBFR ) versus, traditional resistance training (G TRT ) and non-training on the muscle strength and body composition HIV/AIDS participants. Muscle strength was tested at baseline, and on the 6th, 21st and 36th training sessions, using maximal repetition test. Pre- and post-intervention body composition changes were measured by dual-energy X-ray absorptiometry. Resistance training was undertaken three times a week comprising bilateral elbow extension and flexion exercises, unilateral flexion and bilateral knee extension. Changes in strength and body composition (pre- and post-intervention) between groups were evaluated by mixed models of repeated measures, and by paired and unpaired comparisons, considering the Effect Size. All groups were similar at baseline for muscle strength and body composition. Post-intervention, the training groups showed similar, statistically significant increases in muscle strength (G RTBFR =25.7-57.4%; G TRT= 24.5-52.3%) and skeletal muscle tissue (G RTBFR =8.4%; G TRT =8.3%). There was also a significant change in body fat ( p =0.023-0.043), with significant effect sizes for strength and skeletal muscle tissue (0.41-2.27), respectively. These results suggest that both resistance training interventions promoted muscle hypertrophy, body fat reduction and positive impact on muscle strength in people living with HIV/AIDS. Resistance training with blood flow restriction proved to be an effective alternative to include patients with marked physical weakness, unable to engage in regular strength training programme.ClinicalTrials.gov identifier: NCT02783417.

Although ocular toxoplasmosis is a leading cause of posterior uveitis worldwide, there is scarce information about the real-life frequency of ocular lesions, visual outcomes, and risk factors for poor prognosis. We conducted a community-based cross-sectional study with 721 adults living in Cássia dos Coqueiros, Southeast Brazil, consisted of visual acuity measurement, dilated ocular examination, a risk-factor questionnaire, and peripheral blood collection for anti-T. gondii serology. Presumed toxoplasmic lesions were recorded on video and analyzed by experienced and masked ophthalmologists. Ocular toxoplasmosis was determined if at least one suspected lesion was appointed by two graders in the presence of positive anti-T. gondii serology. Forty-eight eyes (n = 42 participants; 6.7% among those with positive anti-T. gondii serology) with ocular toxoplasmosis were found. Most lesions were single (n = 28; 58.3%), peripheral (n = 34; 77.1%) and unilateral (85.7% of participants); no active lesions were found. Older age was associated with lesions larger than one-disc diameter (p = 0.047), and lower social stratum (OR: 2.89; CI 1.2-6.97; p = 0.018) was associated with the presence of toxoplasmic lesions. Although there were no differences in visual acuity between participants and eyes with or without ocular lesions (p > 0.05), unilateral blindness associated with ocular toxoplasmosis was identified in a reduced number of individuals.

Objective: To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes., Design: We present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate., Results: Seventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0-6.0) days for the colchicine group and 6.5 (4.0-9.0) days for the placebo group (p<0.001). Median (IQR) time of hospitalisation was 7.0 (5.0-9.0) days for the colchicine group and 9.0 (7.0-12.0) days for the placebo group (p=0.003). At day 2, 67% versus 86% of patients maintained the need for supplemental oxygen, while at day 7, the values were 9% versus 42%, in the colchicine and the placebo groups, respectively (log rank; p=0.001). Two patients died, both in placebo group. Diarrhoea was more frequent in the colchicine group (p=0.26)., Conclusion: Colchicine reduced the length of both, supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. Once death was an uncommon event, it is not possible to ensure that colchicine reduced mortality of COVID-19., Trial Registration Number: RBR-8jyhxh., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Veras et al.)

Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although the high prevalence of lesions in HIV patients can be explained by the immunosuppressive condition, several studies have reported that natural selection can make C. albicans more virulent in this group of patients. Comparisons of the activity of exoenzymes (phospholipase, proteinase and hemolysin) in C. albicans isolated from HIV-infected and uninfected patients have yielded conflicting results. This study aimed, through a systematic review and meta-analysis, to answer the question: "Is the hydrolytic enzymatic activity of C. albicans, isolated from the oral cavity, different in individuals infected and not infected with HIV?" The question was addressed using the PECO framework: P (Population): children and adults, E (Exposure): HIV infection, C (Comparator): non-HIV-infected patients; O (Outcomes): exoenzymes activity i.e. phospholipase, proteinase and hemolysin. We conducted a systematic search on Pubmed, Embase, Scopus, Livivo, Lilacs, Web of Science, and Science Direct databases, and Google Scholar. The MAStARI tool was used to evaluate the risk of bias in the selected studies. From 2259 studies, 19 were included in this review and 11 comprised the meta-analysis. The activity of phospholipase (M-H = 0.15; Z = 2,76; p = 0.0006) and hemolysin exoenzymes (M-H = 0.07; z = 1,94; p = 0.05) was higher in C. albicans isolated from the oral cavity of HIV-infected patients, whereas the levels of protease activity were not different compared with non-HIV-infected individuals. This study showed a higher phospholipase and hemolysin activity in C. albicans isolates from the oral cavity of HIV-infected patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tuberculosis (TB) is the leading cause of mortality among infectious diseases worldwide. The study of molecular targets for therapy and diagnosis suggested that Notch signaling is an important pathway for the maintenance of the immune response during Mycobacterium tuberculosis (Mtb) infection. We evaluated the participation of the Notch pathway in the modulation of immune response during Mtb infection, and observed that patients with active TB had increased DLL4 expression in intermediate and non-classic monocytes. Further, patients with moderate and advanced lung injury have higher Notch1 expression in CD4 + T cells when compared to patients with a minimal lung injury. When we considered the severity of disease in active TB patients, the expression of the DLL4 in intermediate monocytes and the expression of Notch1 in CD4 + T cells are positively correlated with the degree of lung injury. In vitro, PBMCs treated with the Notch pharmacological inhibitor reduced the production of IL-17A and IL-2, whereas anti-hDLL4 treatment promoted a significant increase in TNF-α and phagocytosis. We suggest that Notch1 and DLL4 are associated with immune response activation in human tuberculosis, and can be a novel target to be exploited in the future in the searching of biomarkers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR-TB., Methods: Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out., Results: It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06-15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44-6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87-2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91-3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44-2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14-1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10-1.46) were associated with MDR-TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25-1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17-1.93) and that had more than 20.16% of their population with income between ¼ and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30-1.87) were also related to the MDR-TB., Conclusions: Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR-TB, avoiding the risks expressed regarding drug resistance expansion., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: Tuberculosis (TB) transmission in healthcare facilities is still a concern in low-income countries, where airborne isolation rooms are scarce due to high costs. We evaluated the use of single GeneXpert MTB/RIF, the molecular Mycobacterium tuberculosis (MTB) DNA and resistance to rifampicin (RIF) test, as an accurate and faster alternative to the current criteria of 3 negative acid-fast bacilli (AFB) smears to remove patients from airborne isolation., Methods: In this real-world investigation, we evaluated the impact of a single GeneXpert MTB/RIF on the decision making for discharging patients from respiratory isolation. We enrolled patients with suspected pulmonary TB in a public hospital that provides care for high-complexity patients in Brazil. We studied the performance, costs, and time saved comparing the GeneXpert MTB/RIF with AFB smears., Results: We enrolled 644 patients in 3 groups based on the number of AFB smears performed (1, 2, and 3, respectively) on respiratory specimens. GeneXpert MTB/RIF demonstrated good performance compared to AFB smear to rule out TB in all groups. The negative predictive value for AFB smear was 94% (95% confidence interval [CI], 0.90-0.97) and 98% (95% CIs, 0.94-0.99) for GeneXpert MTB/RIF in G3. The isolation discharge based on 3 AFB smears took 84 hours compared to 24 hours with GeneXpert MTB/RIF, which represents 560 patient-days saved in the isolation rooms., Conclusion: A single GeneXpert MTB/RIF is a fast and strong predictor for TB absence in a high-complexity hospital, which is quite similar to results obtained in recent studies in low-burden settings. This molecular test may also increase patient rotation through isolation rooms, with a positive impact in the emergency room and infectious diseases wards.

The HIV/AIDS pandemic still represents an important global health issue. There is no sterilizing cure, therefore a continuous treatment is necessary, which caused the emerged idea of HIV as a chronic inflammatory disease that may also affect healthy aging. Considering that the activation profile of some innate cells such as natural killer cells has previously been associated to HIV progression, it remains to be better defined this activation status of NK cells considering the time of HIV infection. In this study, we characterized NK cell phenotype and function during acute and chronic HIV infection and also investigated markers of immunosenescence in these cells. Our results showed that chronic infected patients remained with elevated levels of some plasma inflammatory molecules (IP-10, sCD14) and a concurrent expansion of the non-functional NK cell subset (CD3 - CD56 - CD16 + ). NK cells from the chronic infected group displayed an activated profile with higher levels of cytokines and chemokines production (TNF-α, IL-12, IFN-α2, IFN-γ, IL-6, RANTES, MCP-1, IL-10, IL-4 and IL-5). The production of these molecules was positively correlated to the time of infection. Moreover, we noted a possible association of higher global DNA methylation frequency of NK cells in two HIV patients in the advanced stage of disease. Chronic infected patients also showed a trend towards higher production of reactive oxygen species by their NK cells which altogether suggest the evolution of these cells to a senescent state that might be further evaluated., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest. Disclosures The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains., Objective: To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique., Methods: Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDR TM plus and MTBDR TM sl., Findings: Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission., Conclusion: WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Delivering bad news is a difficult task for physicians, and medical schools do not always prepare future physicians for this inevitable task., Objective: To examine training in breaking bad news, to improve medical students' competence and confidence in dealing with this important aspect of clinical practice., Methods: An exploratory study using a qualitative approach was done at a Brazilian public university's medical school, which receives 30 medical students per semester. Two focus groups were conducted in 2018, with 15 students per group, before and after the training. The intervention consisted of a 6-month (4 h/wk) course about breaking bad news offered to 30 third-year medical students. The communication course included the perspectives of health care professionals, patients, and their families; the SPIKES protocol and the "ABCDE" mnemonic for delivering bad news; general guidelines; and role-playing/simulation strategies to improve students' skills and reduce their personal limitations., Results: Results of the preintervention focus group demonstrated that only 30% of the students were aware of the importance of breaking bad news and of the existence of specific protocols to guide physicians in these situations. Findings from the postintervention focus group indicated that 90% of students understood the importance and began to apply protocols in their practice., Discussion: Breaking bad news is a challenge for undergraduate medical students. The results of our qualitative study showed that students' perceptions about their capability in delivering bad news increased significantly after regular and focused training. The knowledge, skills, and attitudes acquired strengthened the students' self-reported ability to deal with situations requiring breaking bad news., Conclusion: The activities offered helped students develop communication skills. They made connections between their formal training (communication and cognitive skills) and actual clinical practice in a community-based rotation. The knowledge and skills acquired gave them tools needed to deliver bad news in their future clinical practice.

Over the years, various recommendations have been made in pursuit of controlling resistance to antituberculosis drugs, especially multidrug resistance, in Brazil. Given the importance of standardizing those recommendations, the aim of this study was to describe the main recommendations of the Brazilian guidelines, primarily those related to the treatment and follow-up of cases of tuberculosis. From August through October of 2018, a document search was conducted via the websites of the Brazilian National Ministry of Health, the Brazilian National Tuberculosis Control Program, the JBP, and the Official Gazette of the Federal Republic of Brazil. Data were collected systematically by using a protocol designed specifically for this study. Documents published between 2004 and 2018 were selected. It was possible to understand and trace the history of the measures for the control of multidrug-resistant tuberculosis in Brazil from 2004, when the first documents related to the disease were published, up to 2018, when the second edition of the Brazilian National Guidelines for the Control of Tuberculosis was published. The contents of the documents were analyzed and grouped by case definition, diagnostic criteria, treatment, use of directly observed treatment; mechanisms of social protection for patients; data tools; and organization of care. This analysis allowed us to understand the efforts towards standardizing some measures in Brazil, not only identifying advances in the alignment with international prerogatives (case definition, incorporation of diagnostic technology, and treatment regimens) but also underscoring the need for greater clarity regarding the mechanisms of social protection and the organization of the care provided via the Brazilian health care system.

Introduction: Introduction: currently, there is no consensus regarding accurate and low-cost methods for diagnosing lipodystrophy in people living with HIV/AIDS (PLWHA). The aim of this study was to propose anthropometric cutoff points for the diagnosis of lipodystrophy among PLWHA. Methods: we included 106 PLWHA (men = 65, women = 41) who are under antiretroviral therapy and have been clinically classified into either a "lipodystrophy" or "non-lipodystrophy" group. Anthropometric measurements included 19 regions of body perimeters and 6 skinfold thickness measures. The Youden index was used to establish anthropometric cutoff points for the diagnosis of lipodystrophy, using the mean values of the anthropometric data (referred to as "original") along with the "Z index" (ZI) values, which were adjusted by the "Phantom Strategy." The cutoff points were proposed when "original" anthropometric measurements and ZI values had a statistical significance of p < 0.01 and an area under the curve (AUC) higher than 70%. The size effect was assessed to verify the influence of lipodystrophy on each anthropometric measure. Results: our data analysis proposes sex-specific cutoff points for the diagnosis of lipodystrophy in PLWHA - 17 points using the "original" anthropometric measurements, and 20 using the ZI values (average effect size between 1.0 and 1.1, and AUC = 76.7% and 78%). Conclusions: our study proposes accurate cutoff points for the diagnosis of lipodystrophy using "original" anthropometric measurements and ZI values adjusted by the "Phantom Strategy." Our findings support the use of anthropometric measurements as a simplified method for diagnosing lipodystrophy and monitoring body composition alterations in people living with HIV/AIDS.

Introduction: Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country., Methods: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed., Results: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases., Conclusions: Beira and Mozambique share the same population genetic structure of M. tuberculosis.

Objective: to analyze the temporal trend, identify the factors related and elaborate a predictive model for unfavorable treatment outcomes for multidrug-resistant tuberculosis (MDR-TB)., Methods: Retrospective cohort study with all cases diagnosed with MDR-TB between the years 2006 and 2015 in the state of São Paulo. The data were collected from the state system of TB cases notifications (TB-WEB). The temporal trend analyzes of treatment outcomes was performed through the Prais-Winsten analysis. In order to verify the factors related to the unfavorable outcomes, abandonment, death with basic cause TB and treatment failure, the binary logistic regression was used. Pictorial representations of the factors related to treatment outcome and their prognostic capacity through the nomogram were elaborated., Results: Both abandonment and death have a constant temporal tendency, whereas the failure showed it as decreasing. Regarding the risk factors for such outcomes, using illicit drugs doubled the odds for abandonment and death. Besides that, being diagnosed in emergency units or during hospitalizations was a risk factor for death. On the contrary, having previous multidrug-resistant treatments reduced the odds for the analyzed outcomes by 33%. The nomogram presented a predictive model with 65% accuracy for dropouts, 70% for deaths and 80% for failure., Conclusions: The modification of the current model of care is an essential factor for the prevention of unfavorable outcomes. Through predictive models, as presented in this study, it is possible to develop patient-centered actions, considering their risk factors and increasing the chances for cure.

Lineage 1 (L1) is one of seven Mycobacterium tuberculosis complex (MTBC) lineages. The objective of this study was to improve the complex taxonomy of L1 using phylogenetic SNPs, and to look for the origin of the main L1 sublineage prevalent in Para, Brazil. We developed a high-throughput SNPs-typing assay based on 12-L1-specific SNPs. This assay allowed us to experimentally retrieve SNP patterns on nine of these twelve SNPs in 277 isolates previously tentatively assigned to L1 spoligotyping-based sublineages. Three collections were used: Pará-Brazil (71); RIVM, the Netherlands (102), Madagascar (104). One-hundred more results were generated in Silico using the PolyTB database. Based on the final SNPs combination, the samples were classified into 11 clusters (C1-C11). Most isolates within a SNP-based cluster shared a mutual spoligotyping-defined lineage. However, L1/EAI1-SOM (SIT48) and L1/EAI6-BGD1 (SIT591) showed a poor correlation with SNP data and are not monophyletic. L1/EAI8-MDG and L1/EAI3-IND belonged to C5; this result suggests that they share a common ancestor. L1.1.3/SIT129, a spoligotype pattern found in SNPs-cluster C6, was found to be shared between Pará/Brazil and Malawi. SIT129 was independently found to be highly prevalent in Mozambique, which suggests a migration history from East-Africa to Brazil during the 16th-18th slave trade period to Northern Brazil., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Effective treatment of tuberculosis (TB) remains a serious public health problem in many countries, including Brazil, especially when considering drug-resistant disease. Xpert MTB/RIF has been implemented in many countries to reduce the time to TB diagnosis and to rapidly detect rifampicin resistance. The study aimed to describe and evaluate Xpert MTB/RIF performance in diagnosing pulmonary TB and rifampicin resistance in a tertiary healthcare facility in Brazil. A cross-sectional study was performed, which included all isolates of confirmed pulmonary TB patients from 2015 to 2018. Both Xpert MTB/RIF and GenoType MTBDR plus assays were performed to detect rifampicin and isoniazid resistance. In addition, isolates with detected resistance to rifampicin and/or isoniazid were analysed by phenotypic testing using MGIT-960 SIRE kit and whole-genome sequencing (WGS) using Illumina MiSeq Sequencing System. 2148 respiratory specimens tested with Xpert MTB/RIF were included: n=1556 sputum, n=348 bronchoalveolar lavage and n=244 gastric washing. The overall Xpert MTB/RIF sensitivity in sputum was 94% and the overall specificity was 98%. The negative predictive value in sputum of all the patients was 99% with a positive predictive value of 89%. The concordance between Xpert MTB/RIF and phenotypic susceptibility test was 94.1%, while its concordance with WGS was 78.9%. Xpert MTB/RIF is a rapid and accurate diagnostic strategy for pulmonary TB, which can contribute to improvement in TB control. However, detection of rifampicin resistance might be associated with false-positive results., Competing Interests: Conflict of interest: C.S. Feliciano reports grants from FAPESP during the conduct of the study. Conflict of interest: L.C.B. Menon has nothing to disclose. Conflict of interest: L. Anselmo has nothing to disclose. Conflict of interest: A. Dippenaar has nothing to disclose. Conflict of interest: R.M. Warren has nothing to disclose. Conflict of interest: W.A. Silva Jr reports grants from FAPESP during the conduct of the study. Conflict of interest: V.R. Bollela reports grants from FAPESP during the conduct of the study.

Introduction: The prevalence of Toxoplasma gondii infection varies markedly among different populations, especially depending on factors related to socioeconomic development and eating habits. Cássia dos Coqueiros is a small city in Brazil with rural characteristics and increased risk factors traditionally associated with T. gondii infection., Methods: We carried out a cross-sectional study involving 970 inhabitants aged 18 years or more, selected from patients of the local health unit and home visits in urban and rural areas. Each participant completed a survey with questions regarding demographic, socioeconomic, and risk factors for toxoplasmosis. Blood samples from participants were tested for presence of IgG and IgM antibodies against T. gondii using a chemiluminescent microparticle immunoassay., Results: The prevalence of IgG and IgM antibodies was 62.3% and 2.5%, respectively. Variables that proved to be independent predictors of infection were age, low levels of education, and previous diagnosis of toxoplasmosis., Conclusions: The high prevalence of toxoplasmosis serological markers in this adult population highlights the need to promote preventive practices, especially those directed toward women of childbearing age, in this part of Brazil.

Following publication of the original article [1], one of the authors flagged that unfortunately their last name, Doltario, was incorrectly spelled as 'Dotrário'. This has since been corrected in the original article [1].

Background: Body fat redistribution and metabolic abnormalities found in HIV patients receiving highly active antiretroviral therapy (HAART) contribute to an atherogenic profile, increasing cardiovascular disease risk., Objective: We aimed to evaluate adiposity measures/indexes and propose cutoffs associated with predictors of cardiovascular disease risk in HIV patients on HAART., Design: To evaluate cardiovascular disease risk in this cross-sectional study, we conducted electrocardiogram exams and stress electrocardiography, measured the ankle brachial index and blood pressure arterial hypertension, conducted lipid biochemical tests, and measured blood glucose. We measured circumferences [waist (WC), hip, thigh, calf, neck, trunk] and skinfold thicknesses (biceps, triceps, subscapular, suprailiac), conducted bioelectrical impedance analysis (BIA), and calculated indexes [body mass index, waist-to-hip ratio, waist-to-thigh ratio, waist-to-calf ratio, waist-to-height ratio (WHtR), trunk-to-arm ratio, body mass index corrected for body fat mass, Body Adiposity Index, conicity index, body shape index, fat mass (percentage), and phase angle]. For evaluating the performance of all adiposity measures/indexes, we used receiver operating characteristic (ROC) curves., Results: Measures of central adiposity WC and WHtR showed the best performances-WC area under the curve (AUC) for men: 0.83 (95% CI: 0.78, 0.89; P < 0.05); WC AUC for women: 0.86 (95% CI: 0.81, 0.91; P < 0.05); WHtR AUC for men: 0.83 (95% CI: 0.78, 0.88; P < 0.05); and WHtR AUC for women: 0.85 (95% CI: 0.80, 0.91; P < 0.05). All adiposity measures/indexes presented different cutoffs from those proposed for the HIV seronegative population. The cutoffs for WC were 87.75 cm (sensitivity: 82.2%; specificity: 75.5%) for men and 90.5 cm (sensitivity: 84.0%; specificity: 73.0%) for women., Conclusions: The measures/indexes of central adiposity presented excellent associations with predictors of cardiovascular disease risk, and the use of the cutoffs proposed in the present study aims to contribute to the early identification of increasing risk of cardiovascular diseases, enabling interventions. This trial was registered at the Brazilian clinical trials registry Registro brasileiro de ensaios clínicos (Rebec) as RBR-9rcxbq.

Background: The fast and accurate diagnosis of drug-resistant tuberculosis (DR-TB) is critical to reducing the spread of disease. Although commercial genotypic drug-susceptibility tests (DST) are close to the goal, they are still not able to detect all relevant DR-TB related mutations. Whole genome sequencing (WGS) allows better comprehension of DR-TB with a great discriminatory power. We aimed to evaluate WGS in M. tuberculosis isolates compared with phenotypic and genotypic DST., Methods: This cross-sectional study evaluated 30 isolates from patients with detected DR-TB in Brazil and Mozambique. They were evaluated with phenotypic (MGIT-SIRE™) and genotypic (Xpert-MTB/RIF™, Genotype-MTBDRplus™, and MTBDRsl™) DST. Isolates with resistance to at least one first- or second-line drug were submitted to WGS and analyzed with TB profiler database., Results: WGS had the best performance among the genotypic DST, compared to the phenotypic test. There was a very good concordance with phenotypic DST for rifampicin and streptomycin (89.6%), isoniazid (96.5%) and ethambutol (82.7%). WGS sensitivity and specificity for detection resistance were respectively 87.5 and 92.3% for rifampicin; 95.6 and 100% for isoniazid; 85.7 and 93.3% for streptomycin while 100 and 77.2% for ethambutol. Two isolates from Mozambique showed a Val170Phe rpoB mutation which was neither detected by Xpert-MTB/RIF nor Genotype-MTBDRplus., Conclusion: WGS was able to provide all the relevant information about M. tuberculosis drug susceptibility in a single test and also detected a mutation in rpoB which is not covered by commercial genotypic DST., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus . In this context, bioactive lipids such as prostaglandin (PG)E 2 and leukotriene (LT)B 4 modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB 4 , PGE 2 , and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE 2 /cAMP/IL-1β release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB 4 , which represses the PGE 2 /cAMP/IL-1β axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1β.