Publications by authors named "Mariana Araujo-Pereira"

15 Publications

  • Page 1 of 1

Determinants of losses in the latent tuberculosis infection cascade of care in Brazil.

BMJ Glob Health 2021 Sep;6(9)

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil

Introduction: Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil.

Methods: Close contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6-24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Multivariable regressions were used to identify determinants of losses in the LTBI cascade.

Results: Among 4145 TB contacts initially identified, 1901 were examined (54% loss). Among those examined, 933 were people living with HIV, ≤5 years old and/or had positive IGRA results, and therefore had a recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (54% of those initiating; 26% of those in whom treatment was recommended) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy and black/ (brown) race were independently associated with losses in the cascade.

Conclusion: There were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts of low socioeconomic status and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjgh-2021-005969DOI Listing
September 2021

Tuberculosis Burden and Determinants of Treatment Outcomes According to Age in Brazil: A Nationwide Study of 896,314 Cases Reported Between 2010 and 2019.

Front Med (Lausanne) 2021 27;8:706689. Epub 2021 Jul 27.

Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.

Approximately 1.4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide public health policy implementation and clinical management to improve outcomes. We obtained data from the national tuberculosis case registry; data were reported to the Brazilian National Program (SINAN) between 2010 and 2019. Clinical and epidemiologic variables were compared between age groups (child: <10 years, young: 10-24years, adult: 25-64years, and elderly: ≥65years). Univariate comparisons were performed together with second-generation -values. We applied a backward stepwise multivariable logistic regression model to identify characteristics in each age group associated with unfavorable TB treatment outcomes. There were 896,314 tuberculosis cases reported during the period. Tuberculosis incidence was highest among adult males, but the young males presented the highest growth rate during the period. Directly observed therapy (DOT) was associated with protection against unfavorable outcomes in all age groups. The use of alcohol, illicit drugs, and smoking, as well as occurrence of comorbidities, were significantly different between age groups. Lack of DOT, previous tuberculosis, race, location of tuberculosis disease, and HIV infection were independent risk factors for unfavorable outcome depending on the age group. The clinical and epidemiological risk factors for unfavorable tuberculosis treatment outcomes varied according to age in Brazil. DOT was associated with improved outcomes in all age groups. Incidence according to age and sex identified adults and young males as the groups that need prevention efforts. This supports implementation of DOT in all populations to improve tuberculosis outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.706689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354381PMC
July 2021

Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock.

Sci Rep 2021 Jul 26;11(1):15149. Epub 2021 Jul 26.

Laboratory of Toxinology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, 21040-900, Brazil.

Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via proteomic profiling. The acute stage of septic shock was associated with an impaired inflammatory phenotype, indicated by the down-regulation of MHC class II molecules and proinflammatory cytokine pathways. Simultaneously, there was an up-regulation of glycolysis enzymes and a decrease in proteins related to the citric acid cycle and oxidative phosphorylation. On the other hand, the restoration of immunocompetence was the hallmark of recovering patients, in which an upregulation of interferon signaling pathways was a notable feature. Our results provide insights into the immunopathology of sepsis and propose that, pending future studies, immunometabolism pathway components could serve as therapeutic targets in septic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-94474-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313678PMC
July 2021

Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study.

Front Immunol 2021 2;12:661934. Epub 2021 Jul 2.

Programa Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.

Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.

Results: Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (10/mm) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (10/mm) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (10/mm) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).

Conclusion: Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.661934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284392PMC
July 2021

Impact of HIV status on systemic inflammation during pregnancy.

AIDS 2021 Jul 8. Epub 2021 Jul 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA Department of Medicine, Weill Cornell Medical College, New York, USA Department of Biostatistics, Columbia University Mailman School of Public Health, New York, USA Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India Byramjee-Jeejeebhoy Government Medical college-Johns Hopkins University Clinical Research Site, Pune, India Instituto Goncalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil Multinational Organization Network Sponsoring Translational and Epidemiological Research, (MONSTER) Initiative, Salvador, Brazil Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, India Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Objective: There are limited studies on the association of HIV infection with systemic inflammation during pregnancy.

Design: A cohort study (N = 220) of pregnant women with HIV (N = 70) (all on antiretroviral therapy) and without HIV (N = 150) were enrolled from an antenatal clinic in Pune, India.

Methods: The following systemic inflammatory markers were measured in plasma samples using immunoassays: soluble CD163 (sCD163), soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), interferon-β (IFNβ), interferon-γ (IFNγ), interleukin (IL)-1β, IL-6, IL-13, IL-17A and tumor necrosis factor α (TNFα). Generalized estimating equation (GEE) and linear regression models were used to assess the association of HIV status with each inflammatory marker during pregnancy and by trimester, respectively.

Results: Pregnant women with HIV had higher levels of markers for gut barrier dysfunction (I-FABP), monocyte activation (sCD14) and markers of systemic inflammation (IL-6 and TNFα), but surprisingly lower levels of AGP, an acute phase protein, compared to pregnant women without HIV, with some trimester-specific differences.

Conclusions: Our data show that women with HIV had higher levels of markers of gut barrier dysfunction, monocyte activation and systemic inflammation. These markers, some of which are associated with preterm birth, might help explain the increase in adverse birth outcomes in women with HIV and could suggest targets for potential interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000003016DOI Listing
July 2021

The Effect of Diabetes and Prediabetes on Mycobacterium tuberculosis Transmission to Close Contacts.

J Infect Dis 2021 May 19. Epub 2021 May 19.

Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.

Background: It is unknown whether dysglycemia is associated with M. tuberculosis transmission.

Methods: We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON-positive and QuantiFERON-conversion.

Results: There were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that TB-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked, were independently associated with QuantiFERON-positive in contacts at baseline. DM, persistent cough, AFB-positive and pulmonary cavities in TB source cases were associated with QuantiFERON-conversion.

Conclusion: Contacts of persons with pulmonary TB and dysglycemia were at increased risk of being QuantiFERON-positive at baseline or month 6. Increased focus on such close contacts could improve TB control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiab264DOI Listing
May 2021

Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial.

Front Immunol 2020 4;11:602589. Epub 2021 Feb 4.

Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.

Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.602589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889506PMC
June 2021

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection.

Front Immunol 2020 27;11:587617. Epub 2021 Jan 27.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States.

Background: Recent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ . LTBI-). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.

Methods: We conducted a cohort study of 155 LTBI+ and 65 LTBI- pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFN, CRP, AGP, I-FABP, IFN, IL-1, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.

Results: Study population was a median age of 23 (Interquartile range: 21-27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.

Conclusions: Our data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI- women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.587617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873478PMC
July 2021

Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV.

Life (Basel) 2021 Jan 18;11(1). Epub 2021 Jan 18.

Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil.

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11010065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831327PMC
January 2021

Association between neurofibromatosis type 1 and cerebrovascular diseases in children: A systematic review.

PLoS One 2021 4;16(1):e0241096. Epub 2021 Jan 4.

Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.

Background: Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular damage. Although not commonly recognized in the context of NF-1, cerebrovascular disease (CVD), can be often present since childhood and diagnosed just later in life. When present, NF-1-associated CVD clinical manifestations may include headache, cognitive deficits and ultimately aneurysm rupture, causing death. Thus, CVD plays an important role in the clinical manifestations, disease severity and prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD in children.

Methods: Two independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: "neurofibromatosis type 1", "Von Recklinghausen's disease", "children", "adolescents", "stroke", "Moyamoya disease", "vascular diseases", "cerebrovascular disorders", "aneurysm" and "congenital abnormalities". Studies focused on assessing the development of CVD in children with NF-1 were included.

Results: Seven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic.

Conclusion: The available evidence suggests that CVDs are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, improved prognosis was observed when imaging tests were performed to screen for cerebrovascular alterations early during the clinical investigation. Early diagnosis of CVD in NF-1 patients foster implementation of timely interventions, directly impacting clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241096PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781472PMC
April 2021

Association of Vegetable and Animal Flesh Intake with Inflammation in Pregnant Women from India.

Nutrients 2020 Dec 8;12(12). Epub 2020 Dec 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.

In pregnant women, studies are lacking on the relationship of vegetable and animal flesh (poultry, red meat and seafood) intake with inflammation, especially in low- and middle-income countries. We conducted a cohort study of pregnant women receiving antenatal care at BJ Medical College in Pune, India. The dietary intake of pregnant women was queried in the third trimester using a validated food frequency questionnaire. Twelve inflammatory markers were measured in plasma samples using immunoassays. Only 12% of the study population were vegetarians, although animal flesh intake levels were lower compared to Western populations. In multivariable models, higher intakes of total vegetables were associated with lower levels of the T-helper (Th) 17 cytokine interleukin (IL)-17a ( = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) ( = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels ( = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 ( = 0.03), and higher seafood was associated with lower IL-13 ( = 0.005). Our data from pregnant women in India suggest that a higher quality diet emphasizing vegetables and with some animal flesh is associated with lower inflammation. Future studies should confirm these findings and test if modulating vegetables and animal flesh intake could impact specific aspects of immunity and perinatal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12123767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762525PMC
December 2020

Novel stepwise approach to assess representativeness of a large multicenter observational cohort of tuberculosis patients: The example of RePORT Brazil.

Int J Infect Dis 2021 Feb 14;103:110-118. Epub 2020 Nov 14.

Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil; Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil; Curso de Medicina, Centro Universitário Faculdade de Tecnologia e Ciências (UniFTC), Salvador, Brazil; Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Curso de Medicina, Universidade Salvador (UNIFACS), Laureate University, Salvador, Brazil. Electronic address:

Background: A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important.

Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts.

Findings: A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts.

Conclusions: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.11.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959330PMC
February 2021

Impact of Persistent Anemia on Systemic Inflammation and Tuberculosis Outcomes in Persons Living With HIV.

Front Immunol 2020 24;11:588405. Epub 2020 Sep 24.

Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Tuberculosis (TB) is associated with systemic inflammation and anemia, which are aggravated in persons living with HIV (PLWH). Here, we characterized the dynamics of hemoglobin levels in PLWH coinfected with TB undergoing antitubercular therapy (ATT). We also examined the relationships between anemia and systemic inflammatory disturbance as well as the association between persistent anemia and unfavorable clinical outcomes. Data on several blood biochemical parameters and on blood cell counts were retrospectively analyzed in a cohort of 256 TB/HIV patients from Brazil during 180 days of ATT. Multidimensional statistical analyses were employed to profile systemic inflammation of patients stratified by anemia status (hemoglobin levels <12 g/dL for female and <13.5 g/dL for male individuals) prior to treatment and to perform prediction of unfavorable outcomes, such as treatment failure, loss to follow up and death. We found that 101 (63.63%) of patients with anemia at pre-ATT persisted with such condition until day 180. Such individuals exhibited heightened degree of inflammatory perturbation (DIP), which in turn was inversely correlated with hemoglobin levels. Recovery from anemia was associated with increased pre-ATT albumin levels whereas persistent anemia was related to higher total protein levels in serum. Multivariable regression analysis revealed that lower baseline hemoglobin levels was the major determinant of the unfavorable outcomes. Our findings demonstrate that persistent anemia in PLWH during the course of ATT is closely related with chronic inflammatory perturbation. Early intervention to promote recovery from anemia may improve ATT outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.588405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541849PMC
July 2021

webCEMiTool: Co-expression Modular Analysis Made Easy.

Front Genet 2019 6;10:146. Epub 2019 Mar 6.

Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

Co-expression analysis has been widely used to elucidate the functional architecture of genes under different biological processes. Such analysis, however, requires substantial knowledge about programming languages and/or bioinformatics skills. We present webCEMiTool, a unique online tool that performs comprehensive modular analyses in a fully automated manner. The webCEMiTool not only identifies co-expression gene modules but also performs several functional analyses on them. In addition, webCEMiTool integrates transcriptomic data with interactome information (i.e., protein-protein interactions) and identifies potential hubs on each network. The tool generates user-friendly html reports that allow users to search for specific genes in each module, as well as check if a module contains genes overrepresented in specific pathways or altered in a specific sample phenotype. We used webCEMiTool to perform a modular analysis of single-cell RNA-seq data of human cells infected with either Zika virus or dengue virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2019.00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414412PMC
March 2019

Rapid molecular test for tuberculosis: impact of its routine use at a referral hospital.

J Bras Pneumol 2018 Apr;44(2):112-117

Departamento de Medicina, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.

Objective: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia.

Methods: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation.

Results: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%.

Conclusions: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/s1806-37562017000000201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044659PMC
April 2018
-->