Outcomes of severely ill patients with AIDS treated with efavirenz or dolutegravir: a multicenter, observational study.

Background: Currently, integrase inhibitors (INIs)-based ART regimens are the preferred initial therapy for AIDS patients. There is scarce information on the use of dolutegravir (DTG) among late-presenter people living with HIV (PLHIV). Objectives: To compare the effect of DTG- or efavirenz (EFV)-based regimens on the outcomes of patients with advanced AIDS. Methods: We compared two cohorts of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/mL) starting therapy with DTG-based (2018-2021, prospective cohort) or EFV-based regimens (2013-2016, retrospective cohort) from five Brazilian cities. The main endpoints were early (all-cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count, and changes in initial therapy (for any reason). Results: We included all eligible patients in a consecutive way (in both groups) until we reached 92 individuals per arm. The median baseline CD4 count (20 vs. 21 cells/mL) and the median HIV plasma viral load (5.5 copies/mL log10) were identical across the groups. Viral suppression rates were higher in the DTG group than in the EFV group at 24 (67.4% vs. 42.4%,) and 48 weeks (65.2% vs. 45.7%, p < 0.001 for both comparisons). More patients in the DTG group presented with CD4 > 200 cells/mL compared to the EFV group at 48 weeks (45% vs. 29%, p = 0.03). Treatment changes (ITT, M = F) were significantly more frequent in the EFV group (1% vs. 17%, p < 0.0001). The relative mortality rate was 25% lower in the DTG group, but without statistical significance. Conclusion: We detected a higher rate of virological suppression and greater treatment durability in patients with advanced AIDS treated with DTG than in those treated with EFV.

Association between increased Subcutaneous Adipose Tissue Radiodensity and cancer mortality: Automated computation, comparison of cancer types, gender, and scanner bias.

PURPOSE: Body composition analysis using computed tomography (CT) is proposed as a predictor of cancer mortality. An association between subcutaneous adipose tissue radiodensity (SATr) and cancer-specific mortality was established, while gender effects and equipment bias were estimated. METHODS: 7,475 CT studies were selected from 17 cohorts containing CT images of untreated cancer patients who underwent follow-up for a period of 2.1-118.8 months. SATr measures were collected from published data (n = 6,718) or calculated according to CT images using a deep-learning network (n = 757). The association between SATr and mortality was ascertained for each cohort and gender using the p-value from either logistic regression or ROC analysis. The Kruskal-Wallis test was used to analyze differences between gender distributions, and automatic segmentation was evaluated using the Dice score and five-point Likert quality scale. Gender effect, scanner bias and changes in the Hounsfield unit (HU) to detect hazards were also estimated. RESULTS: Higher SATr was associated with mortality in eight cancer types (p < 0.05). Automatic segmentation produced a score of 0.949 while the quality scale measurement was good to excellent. The extent of gender effect was 5.2 HU while the scanner bias was 10.3 HU. The minimum proposed HU change to detect a patient at risk of death was between 5.6 and 8.3 HU. CONCLUSIONS: CT imaging provides valuable assessments of body composition as part of the staging process for several cancer types, saving both time and cost. Gender specific scales and scanner bias adjustments should be carried out to successfully implement SATr measures in clinical practice.

Multi-center Integrating Radiomics, Structured Reports, and Machine Learning Algorithms for Assisted Classification of COVID-19 in Lung Computed Tomography.

Purpose: To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans. Methods: Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building (n = 73), and another for model validation (n = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using Cohen's Kappa agreement coefficient. Results: Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial. Conclusion: Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans.

The impact of 10-valent pneumococcal conjugate vaccine upon hospitalization rate of children with pneumonia in different Brazilian administrative regions.

BACKGROUND: Streptococcus pneumoniae is the most frequent bacterial causative agent of pneumonia. Due to its significant contribution to the morbidity and mortality profile and the country's economy, the 10-valent pneumococcal vaccine (PCV10) was introduced in Brazil in 2010. Brazil is divided into five administrative regions which differ in social-economic indices among each other. Estimates of PCV10 impact on hospitalization rates due to pneumonia stratified by distinct Brazilian regions are limited. We assessed this issue. METHODS: This is a population-based ecological investigation. Data about hospitalizations due to pneumonia, asthma or urinary tract infection (UTI) among patients aged under 20 years in the pre-exposure (2003-2009) and in the post-exposure (2011-2017) periods were retrieved from the National Health System - Hospital Information System (SIH-SUS) database. The total resident population by age group in each year was retrieved from the Brazilian Institute for Geography and Statistics database. Hospitalization rates were estimated for each Brazilian region and the rates obtained in the pre-exposure and in the post-exposure periods were compared by Prais-Winsten regression. The Human Development Index (HDI) evolved differently in the distinct regions during the study period. RESULTS: Overall, hospitalization rates due to pneumonia declined by 34.5%. Similar trends were observed for hospitalization rates due to asthma and UTI. The same pattern was observed in each Brazilian region. However, the North region was the only one that presented an exponential incidence decline pattern, which could be explained by PCV10 implementation (declined by 10.8% in the quadratic regression, p < 0.01). Only in the North region, significant decline was observed among patients aged 0-4 years (-12.5%; p = 0.01), 5-9 years (-38.5%; p < 0.01) or 10-14 years (-10.7%; p = 0.03). CONCLUSION: Significant variation in the downward trend of hospitalization rate was only found in the North region, which evolved from very low HDI in 2003; medium HDI in 2010 to high HDI in 2017.

Determinants of losses in the latent tuberculosis cascade of care in Brazil: A retrospective cohort study.

BACKGROUND: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. METHODS: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. RESULTS: From a total of 1180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. CONCLUSIONS: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care.

Impact of the change in the antitubercular regimen from three to four drugs on cure and frequency of adverse reactions in tuberculosis patients from Brazil: A retrospective cohort study.

BACKGROUND: The Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines. METHODS: A retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil. FINDINGS: TB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10-2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups. CONCLUSION: The patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

Immune Activation, Proinflammatory Cytokines, and Conventional Risks for Cardiovascular Disease in HIV Patients: A Case-Control Study in Bahia, Brazil.

BACKGROUND: Cardiovascular events (CVE) are an increasing cause of morbi-mortality for HIV patients. The antiretroviral therapy (ART), persistent immune activation, and life style are factors that can increase CVE for such patients. We performed a case-control study to evaluate the role of coinfections and immune markers associated with CVE. METHODS: We included patients under ART, with undetectable plasma viral load ≥12 months. Patients presenting any condition of risk for CVE were considered cases, and those without CVE risk conditions were controls. History of viral infections (Epstein-Barr virus, hepatitis C virus, hepatitis B virus, and cytomegalovirus), exposure to antiretroviral drugs, time since HIV diagnosis/under ART, and life style (demographics, weight, smoking, alcohol, and illicit drug use) were assessed. CD4/CD8 nadir and current counts, nadir and current CD4/CD8 ratio, immune activation markers (CD4CD38HLADR, CD8CD38HLADR), and serum levels of eight cytokines [IL-2, IL-4, IL-6, IL-10, tumoral necrosis factor-alpha (TNF-α), interferon gamma, macrophage inflammatory proteins 1 alpha, and interferon-inducing protein (IP-10)] were measured. RESULTS: Two-thirds of patients were males. Cases (N = 106) were older (52.8 vs 49.5 years, p = 0.002), had higher levels of creatinine (0.97 vs 0.87 mg/dL, p = 0.002) and IL-6 (0.67 vs 0.52 pg/mL, p = 0.04) than controls (N = 114). There was no difference between groups regarding frequency of CD4CD39HLADR+ or CD8CD38HLADR+ cells. We found a significant correlation (all patients) between increased frequency of CD4CD38HLADR+ cells and levels of IP-10 (r = 0.171, p = 0.02) and TNF-α (r = 0.187, p = 0.01). Levels of IL-6 (r = 0.235, p = 0.02), TNF-α (r = 0.267, p = 0.01), and IP-10 (r = 0.205, p = 0.04) were correlated with CD4CD38HLADR+ cells, in controls. Higher frequency of CD4CD38HLADR+ cells was also correlated with levels of IP-10 (r = 0.271, p = 0.04) in patients presenting with arterial hypertension. Frequency of CD4CD38HLADR+ cells was negatively correlated with levels of IL-2 (r = -0.639, p = 0.01) and IL-6 (r = -0.0561, p = 0.03) in patients with hypercholesterolemia. No association was detected between viral infections or smoking/alcohol use and immune activation markers. CONCLUSION: Our results indicate IL-6 levels are associated with increased CV risk. Activated CD4+ T cells were associated with increased levels of proinflammatory cytokines.

Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+874 A>T polymorphism

ABSTRACT Introduction Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-γ production can be influenced by genetic polymorphisms, of which the IFNG + 874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG + 874 A/T polymorphism on interferon-gamma test performance. Methods Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG + 874 genotype and the IFN-γ levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB® Gold In-Tube). Results IFN-γ production was not influenced by the IFNG + 874 genotype, regardless of antigen or mitogen-based stimulation, which suggests that other genes may influence IFN-γ production in response to mycobacteria. The IFNG + 874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. Conclusions The IFNG + 874 polymorphism was not shown to influence QuantiFERON-TB® Gold In-Tube test performance in an admixed population from northeastern Brazil.

Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+874 A>T polymorphism.

INTRODUCTION: Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-γ production can be influenced by genetic polymorphisms, of which the IFNG+874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG+874 A/T polymorphism on interferon-gamma test performance. METHODS: Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG+874 genotype and the IFN-γ levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB® Gold In-Tube). RESULTS: IFN-γ production was not influenced by the IFNG+874 genotype, regardless of antigen or mitogen-based stimulation, which suggests that other genes may influence IFN-γ production in response to mycobacteria. The IFNG+874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. CONCLUSIONS: The IFNG+874 polymorphism was not shown to influence QuantiFERON-TB® Gold In-Tube test performance in an admixed population from northeastern Brazil.

Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women.

Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA <50 copies per mL), in all patients who received at least one dose of study drugs (modified intention-to-treat analysis). Missing information was treated as failure. We assessed safety in all patients. Results We enrolled and randomly assigned treatment to 33 patients (17 in raltegravir group) between June 2015 and June 2017. The study was interrupted by the IRB because a significant difference between arms was detected in an interim analysis. All patients completed follow up at delivery. At delivery, virological suppression was achieved by 13/17 (76.5%) of patients in raltegravir group, versus 4/16 (25.0%) in lopinavir/ritonavir group (RR 3.1, 95% CI: 1.3-7.4). Patients in raltegravir group had significantly higher proportion of virological suppression at 2, 4, and 6 weeks than lopinavir/ritonavir group. Adverse events were most of mild intensity, but patients in lopinavir/ritonavir group had significantly more gastrointestinal adverse events. There was neither discontinuation nor deaths in this trial. Conclusion Raltegravir might be a first-line option for treatment of HIV-infected late-presenting pregnant women.

Impaired TNF, IL-1ß, and IL-17 production and increased susceptibility to Mycobacterium tuberculosis infection in HTLV-1 infected individuals.

IFN-γ and TNF play critical roles in the control of Mycobacterium tuberculosis infection. Despite leading to an exaggerated production of inflammatory cytokines, HTLV-1 infection increases the risk of developing tuberculosis (TB). However, the immune mechanisms accounting for this phenomenon are still unclear. The aim of this study was to evaluate immunological aspects of the HTLV-1/M. tuberculosis co-infection. In this cross-sectional study, the levels of TNF, IL-1ß, and IL-17 were determined by ELISA in the supernatants of either unstimulated or tuberculin purified protein derivative (PPD) stimulated peripheral blood mononuclear cells. Cells from HTLV-1 infected individuals produced lower levels of TNF following PPD stimulation compared to unstimulated cells. IL-1ß and IL-17 production by cells from HTLV-1/M. tuberculosis co-infected individuals was lower than in cells from patients with TB. Impairment in TNF, IL-1ß, and IL-17 production upon stimulation with mycobacterial antigens may contribute to the increased susceptibility to M. tuberculosis infection observed in HTLV-1 infected individuals.

Infection by HTLV-1 Is Associated With High Levels of Proinflammatory Cytokines in HIV-HCV-Coinfected Patients.

OBJECTIVES: HIV, hepatitis C virus (HCV), and human T-cell lymphotropic virus type 1 (HTLV-1) share the same routes of infection, making coinfection by these viruses a frequent finding in endemic areas. However, there is scarce information on the clinical/immunological consequences of triple infection. Coinfection by HTLV-1 is able to modulate cytokine's production in patients with HIV, but there are no data on the immune response of HIV-HCV-HTLV-1-infected patients. METHODS: We compared the plasma levels of 25 different cytokines in patients with HIV-HCV, according to their serostatus to HTLV-1 infection. Eligible patients should be on stable highly active antiretroviral therapy and have undetectable HIV-1 plasma viral load for, at least, 12 months. Cytokines levels were also evaluated by CD4 cells count, rates of sustained virological response (SVR) to previous HCV treatment, frequency of spontaneous HCV clearance, and HCV/IFN-λ3 genotypes. RESULTS: Twenty-five patients (15 coinfected by HIV and HCV, 10 coinfected by HIV, HCV, and HTLV-1) were evaluated. Among the triply infected group, 3 had undetectable HCV viremia (spontaneous clearance). All but one remaining patients were previously treated for HCV, with similar SVR rates (∼29%). Cytokines levels did not differ per HCV/IFN-λ3 genotypes, mean CD4 cells count, age, sex, or SVR. However, patients coinfected by HTLV-1 showed significantly higher levels of IL-1b, IL-2, TNF-α, IFN-γ, MIP-1α, RANTES, and interferon-induced protein 10 (IP-10) than HIV-HCV-coinfected ones. Patients presenting HCV spontaneous clearance had the highest levels of cytokines. CONCLUSIONS: Coinfection by HTLV-1 increases the plasma levels of proinflammatory cytokines of patients with HIV-HCV and can influence the outcomes of coinfected patients.

Increased expression of CD38 and HLADR in HIV-infected patients with oral lesion.

Persistent immune actiation is associated with innadequate immune recovery in HIV-patients. This study assessed the relationship between frequency of expression of cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1 infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral treatment, were divided into three groups, according to the number of CD4+ T cells and CD4+ /CD8+ ratio: adequate, partial, and inadequate immune restauration. All patients underwent full mouth assessments for saliva flow measurement, oral mucosal lesion, periodontal disease, and severity of periodontitis. Immune activation markers levels were compared according to three groups of periodontal disease ("No periodontal disease," "gingivitis," and "periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P = 0.03) were associated with lower CD4+ /CD8+ ratio. Patients with oral mucosal lesions had significantly higher median levels of HLADR and CD38 markers in all T-lymphocytes populations than patients without oral lesions. Patients with gingivitis and with periodontitis presented significantly higher median levels of CD3+ HLADR+ , CD4+ HLADR+ , CD8+ HLADR+ , and CD3+ CD38+ and significantly lower CD4+ /CD8+ ratio than patients with no periodontal disease. Increased levels of HLADR and CD38 expressions in peripheral blood were associated with oral lesions in HIV-positive patients. Periodontal disease was associated with HLADR expression.

Survival Estimates and Mortality Risk Factors in a Cohort of HIV Vertically Infected Individuals in Salvador, Brazil.

BACKGROUND: There are few data on long-term survival of Brazilian children with vertically acquired HIV infection. We assessed survival, mortality risk factors and response to antiretroviral therapy (ART). We compared children with early and late access to care. METHODS: We used Kaplan-Meier survival curves with Log-rank tests to compare survival time and mortality rates of 245 HIV vertically infected children admitted for care during 2002-2014. RESULTS: Total follow-up sum was 1584.4 person-years. Overall survival was 83.9%. Median age at start of ART was 51.6 (18.0-94.2) months, and median age at death was 8.2 (1.7-10.1) years (mortality rate: 1.7/100 person-years). Pneumonia and sepsis were the main causes of death. Male gender, viral load (VL) ≥100,000 copies, severe immunosuppression, moderate/severe symptoms and history of opportunistic infection were associated with higher mortality in bivariate analysis. Only severe symptoms remained associated in multivariate analysis (P = 0.03). There was no difference in mortality in early compared to late access group. Overall, 217 patients received ART; 192 had a recent VL, of which 116 (59.8%) had ≤400 copies. Variables associated with therapeutic failure were as follows: VL ≥100,000 copies, less immune suppression, age <12 months at admission and age <3 years at ART start. CONCLUSIONS: We have a high mortality rate in comparison with developed countries. Although early access did not impact mortality, we detected a trend in favor of early treatment as a protecting factor against mortality. We need to increase adherence to care and treatment, and better drugs to optimize outcomes.

Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil.

BACKGROUND: Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. METHODS: Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. RESULTS: The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. CONCLUSIONS: Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted.

Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study.

BACKGROUND: The rising prevalence of diabetes mellitus (DM) worldwide, especially in developing countries, and the persistence of tuberculosis (TB) as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil. METHODS: We performed a retrospective analysis of a TB patient cohort (treatment naïve) of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT) initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups. RESULTS: DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups. CONCLUSIONS: These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB reference centers in endemic areas.

Lymphocyte subset reference intervals in blood donors from northeastern Brazil.

UNLABELLED: The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαß and TCRγδ+) and NK cells from blood donors in Salvador-Bahia, Brazil. RESULTS: The proportion of included male subjects was 73.7% and the median ages of males (34) and females (35) were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186) cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62) and 24% (9-28), respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03) in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

Utility of recombinant proteins LID-1 and PADL in screening for Mycobacterium leprae infection and leprosy.

BACKGROUND: Despite the widespread use of multidrug therapy, leprosy remains an important public health concern in many regions. Detection is generally limited to clinical exam. METHODS: As a two-tiered active case finding strategy, we used the LID-1 (leprosy IDRI diagnostic-1), and PADL (protein advances for the diagnosis of leprosy) antigens for serological examination of 2526 individuals randomly selected from 10 472 residents in a leprosy hyperendemic area (Cajazeiras, Paraiba, Brazil). Almost all seropositive (95%) and a subset of seronegative (17%) subjects then underwent clinical evaluations. RESULTS: Prevalence of clinically apparent leprosy was 2.3% (19 cases among 834 fully examined individuals). LID-1 and PADL demonstrated a high sensitivity for supporting leprosy diagnosis at 89% and 87%, with positive predictive values (PPV) of 3.5% and 3.7%. The specificity for clinically apparent leprosy was low at 42% and 38%, respectively, and was likely reduced due to the presence of many asymptomatic individuals infected with Mycobacterium leprae. CONCLUSIONS: Our data indicate the utility of the LID-1 and PADL antigens as primary screening tools for the detection of M. leprae infection and identification of leprosy patients. The follow-up of seropositive subjects could clarify the predictive value and utility of detecting anti-LID-1 and PADL antibodies within leprosy control programs.

Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1

BACKGROUND: The human retroviruses HIV-1 and HTLV-1 share the routes of infection with hepatitis viruses B and C. Co-infection by these agents are a common event, but we have scarce knowledge on co-infection by two or more of these agents. OBJECTIVE: To evaluate the characteristics and risk factors for co-infections by HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil. METHODS: In a case-control study we evaluated patients followed in the AIDS and HTLV clinics of Federal University of Bahia Hospital. Clinical and epidemiological characteristics were reviewed, and patients were tested for the presence of serological markers of HBV and HCV infections. HCV-infected patients were tested by PCR to evaluate the presence of viremia. RESULTS: A total of 200 HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were included. HIV-infected patients were more likely to have had more sexual partners in the lifetime than other patients' groups. HIV-HTLV-co-infected subjects were predominantly male. Patients infected by HTLV or co-infected had a significantly higher frequency of previous syphilis or gonorrhea, while HIV infection was mainly associated with HPV infection. Co-infection was significantly associated to intravenous drug use (IVDU). HBV and/or HCV markers were more frequently found among co-infected patients. HBV markers were more frequently detected among HIV-infected patients, while HCV was clearly associated with IVDU across all groups. AgHBs was strongly associated with co-infection by HIV-HTLV (OR = 22.03, 95% CI: 2.69-469.7), as well as confirmed HCV infection (p = 0.001). Concomitant HCV and HBV infection was also associated with retroviral co-infection. Patients infected by HTLV-1 had a lower chance of detectable HCV viremia (OR = 0.04, 95% CI: 0.002-0.85). CONCLUSIONS: Infection by HCV and/or HBV is frequent among patients presenting retroviral infection, but risk factors and prevalence for each infection are distinct for each agent. Retroviral co-infection increases the risk of a positive AgHBs, but HTLV-1 infection seems to increase the likelihood of HCV spontaneous clearance.