The effect of previous SARS-CoV-2 infection on systemic immune responses in individuals with tuberculosis.

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination. Results: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1ß, IL-5, IL-7, and TNF-ß was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1ß was significantly higher in the TB/Prex-SCoV-2 group than the TB group. Conclusion: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.

Anemia and anti-tuberculosis treatment outcome in persons with pulmonary tuberculosis: A multi-center prospective cohort study.

BACKGROUND: Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome. METHODS: Patients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion). RESULTS: Among 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34-45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status. CONCLUSION: Moderate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes.

Impact of adverse drug reactions on the outcomes of tuberculosis treatment.

BACKGROUND: Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes. METHODS: A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information: race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes. RESULTS: 550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR: 2.32; 95% CI:1.34-3.99) and illicit-drug use (OR:2.02; 95% CI:1.15-3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 3/4-ADR (18.36%), especially "liver and biliary system disorders". Lower CD4 counts (<100 cells/uL) were associated with hepatotoxicity (p = 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients. CONCLUSION: Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression.

Immunologic Biomarkers in Peripheral Blood of Persons With Tuberculosis and Advanced HIV.

Introduction: Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV. Methods: A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls. Results: Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint. Conclusion: Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.

Correction: Anemia in tuberculosis cases: A biomarker of severity?

[This corrects the article DOI: 10.1371/journal.pone.0245458.].

Anemia in tuberculosis cases: A biomarker of severity?

INTRODUCTION: Anemia is a common condition at tuberculosis diagnosis, and there is evidence that its prevalence is higher in patients with tuberculosis than in those infected with Mycobacterium tuberculosis and healthy controls. Information about anemia during tuberculosis diagnosis is still scarce in the Brazilian population. The aim of this study was to describe the prevalence of anemia in patients with tuberculosis cared for at a referral center and its association with clinical forms of tuberculosis and other characteristics of these patients. MATERIALS AND METHODS: This was a retrospective cross-sectional study of tuberculosis patients diagnosed from January 2015 to December 2018 at the Clinical Research Laboratory on Mycobacteria (LAPCLIN-TB) of Evandro Chagas National Institute of Infectious Diseases (INI)/Oswaldo Cruz Foundation (Fiocruz). A database of an ongoing cohort study underway at this service since 2000 provided the baseline information on tuberculosis cases extracted from a visit template. Exploratory and logistic regression analyses were performed to verify associations between anemia and demographic characteristics, socioeconomic status, clinical conditions, and laboratory results. RESULTS: Of the 328 cases reviewed, 70 were excluded, with258 retained. The prevalence of anemia was 61.2% (27.5% mild, 27.5% moderate and 6.2% severe). Among patients with anemia, 60.8% had normochromic normocytic anemia, and 27.8% showed hypochromic microcytic anemia. In logistic regression analysis, anemia was associated with a history of weight loss >10%, hospitalizations, coinfection with HIV, increased platelet count and microcytosis. Anemia was more frequent in the most severe clinical forms, such as meningeal and disseminated tuberculosis. CONCLUSIONS: Anemia was highly prevalent in tuberculosis patients at diagnosis, predominantly as normochromic normocytic anemia and in mild and moderate forms. It was associated with baseline characteristics and conditions indicative of severe disease, suggesting that anemia could be a biomarker of tuberculosis severity.

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

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.

Cutaneous tuberculosis in Rio de Janeiro, Brazil: description of a series of 75 cases.

BACKGROUND: Brazil is one of the highest tuberculosis (TB) burden countries of the world. Cutaneous tuberculosis (CTB) is a rare form of extrapulmonary manifestation of tuberculosis. This study aimed to describe the clinico-evolutive, laboratory and therapeutic aspects of CTB cases among patients from a cohort with TB in Rio de Janeiro, Brazil. METHODS: Cases of diagnosed CTB with microbiologic confirmation or clinical response to anti-tuberculous treatment associated with positive smear or histopathological findings between the years 2000 and 2016 were selected. RESULTS: Seventy-five patients with CTB were included, most were women (58.7%) with a median age of 42 years. CTB diagnosis was based on culture in only 42.7% of the cases. Scrofuloderma represented 50.7% of the cases, followed by erythema induratum of Bazin (EIB) (18.7%), tuberculous gumma (13.3%), lupus vulgaris (8%), TB verrucosa cutis (4%), orificial TB (2.7%) and associated forms (2.7%). Other TB presentations were pulmonary (22.7%), mammary (6.6%) and osteoarticular (4%). All patients who completed the treatment (97.3%) had their lesions healed. Only two patients (2.6%) needed to change the therapy due to adverse reactions. Fifty percent of EIB patients presented recurrence. CONCLUSIONS: These data highlight the diversity of CTB presentations and the importance of the skin to assist in early identification and treatment of TB. More studies are necessary to improve the knowledge on EIB for a better approach towards these patients, mainly in cases of recurrence.

Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil-ANRS 12274.

Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a (p = 0.025), NKp80 (p = 0.033), and NKG2C (p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2-24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2+/Vδ2- ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6-24). An increase of CD161+ NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.

Predictors of early mortality and effectiveness of antiretroviral therapy in TB-HIV patients from Brazil.

BACKGROUND: The implementation of antiretroviral (ARV) therapy caused a significant decrease in HIV-associated mortality worldwide. Nevertheless, mortality is still high among people living with HIV/AIDS and tuberculosis (TB). ARV-naïve HIV patients coinfected with tuberculosis (TB) have more options to treat both diseases concomitantly. Nevertheless, some TB-HIV patients undertaking ARVs (ARV-experienced) are already failing the first line efavirenz-based regimen and seem to display different response to second line ARV therapy and exhibit other predictors of mortality. METHODS: We performed a retrospective cohort study including 273 patients diagnosed with TB-HIV and treated at a referral center in Rio de Janeiro, Brazil, between 2008 and 2016. Multivariate analysis and Cox regression models were used to evaluate the effectiveness of ARV therapy regimens (viral load [VL] <80 copies from the 4th to 10th months after TB therapy introduction) and to identify predictors of early mortality (100 days after TB therapy initiation) considering ARV-naïve and ARV-experienced patients adjusting for sociodemographic, clinical and therapeutic covariates. FINDINGS: Survival analysis included 273 patients, out of whom 154 (56.4%) were ARV-naïve and 119 (43.6%) were ARV-experienced. Seven deaths occurred within 6 months of anti-TB treatment, 4 in ARV-naïve and 3 in ARV-experienced patients. Multivariate analysis revealed that in ARV-naïve patients, the chance of death was substantially higher in patients who developed immune reconstitution inflammatory syndrome during the study follow up (HR = 40.6, p<0.01). For ARV-experienced patients, similar analyses failed to identify factors significantly associated with mortality. Variables independently associated with treatment failure for the ARV-naïve group were previous TB (adjusted OR [aOR] = 6.1 p = 0.03) and alcohol abuse (aOR = 3.7 p = 0.01). For ARV-experienced patients, a ritonavir boosted. Protease Inhibitor-based regimen resulted in a 2.6 times higher risk of treatment failure compared to the use of efavirenz based ARV regimens (p = 0.03) and High baseline HIV VL (p = 0.03) were predictors of treatment failure. CONCLUSIONS: Risk factors for mortality and ARV failure were different for ARV-naïve and ARV-experienced patients. The latter patient group should be targeted for trials with less toxic and rifampicin-compatible drugs to improve TB-HIV treatment outcomes and prevent death.

Tuberculosis-HIV treatment with rifampicin or rifabutin: are the outcomes different?

BACKGROUND: Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin. OBJECTIVE: Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. METHODS: We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. FINDINGS: There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment (67% versus 18%, p < 0.001) compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated (66,6% versus 36,3%, p = 0.039). CONCLUSIONS: Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies.

Tuberculosis-HIV treatment with rifampicin or rifabutin: are the outcomes different?

BACKGROUND Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin. OBJECTIVE Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. METHODS We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. FINDINGS There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment (67% versus 18%, p < 0.001) compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated (66,6% versus 36,3%, p = 0.039). CONCLUSIONS Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil.

BACKGROUND: Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE: To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS: We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS: Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS: In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Daily 800 mg versus 600 mg Efavirenz for HIV Patients Treating Tuberculosis with a Rifampicin-Based Regimen: An Open Label Randomized Controlled Trial.

OBJECTIVES: Pharmacokinetics studies recommend increasing efavirenz dosage in tuberculosis/HIV patients using rifampicin. We aimed to evaluate efficacy and safety of 600 versus 800 mg of efavirenz in tuberculosis/HIV patients using rifampicin. DESIGN: We conducted an open label, multicentre, randomized trial from 2006 to 2012. The primary outcome was the proportion of undetectable viral load (HIV-VL) within six months. Secondary outcomes were time to achieve primary endpoint, trajectories of HIV-VL, proportion of any adverse events (AE), proportion of severe and serious AE (SSAE), and time to treatment interruption due to SSAE. METHODS: Efavirenz-naïve patients were randomized 30 days after rifampicin-containing regimens initiation to receive 600 (comparison arm) or 800 mg (intervention arm) efavirenz-based regimens and followed-up for 180 days. RESULTS: Sixty-five and 67 participants were respectively included in the comparison and intervention arms with 64.6% (52.5%-65.1%) and 62.7% (50.7%-73.3%) attaining undetectable HIV-VL in six months. Median time to attain undetectable HIV-VL was 70 days in both arms, with HIV-VL overlapping trajectories during follow-up. Cough, acne, and dizziness were more frequent in the intervention arm. SSAE were observed in 19.1% (13.8%-25.8%) and 25.0% (18.9%-33.2%), respectively. Survival curves up to the first SSAE-attributed treatment interruption were similar. None of the differences were statistically significant. CONCLUSION: Efficacy of efavirenz was similar regardless of dosage. Differences regarding safety occurred as mild and transient events, which did not interfere with treatment. Similar efficacy and safety (SSAE) and lower tolerance (minor AE) in the intervention group favour the use of 600 mg efavirenz in patients using rifampicin.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil

BACKGROUND Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

BACKGROUND: Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. METHODS: This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. RESULTS: Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ≥200 cells/mm3. CONCLUSIONS: These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.

Tuberculosis Treatment Outcomes and Factors Associated with Each of Them in a Cohort Followed Up between 2010 and 2014.

Tuberculosis treatment has undergone recent changes in Brazil. Objective. To assess whether favorable outcomes on tuberculosis therapy improved in recent years. Methods. Retrospective observational study, based on primary data of tuberculosis patients, followed at INI-FIOCRUZ, from January 2012 to December 2014. Results. The outcomes observed were as follows: cure (80%), default (14%), treatment failure (5%), and death (1%). HIV infection without antiretroviral therapy [OR 0.34 (0.15-0.79)], tuberculosis diagnosis based on sputum smear [OR 0.22 (0.07-0.74)], drug use [OR 0.22 (0.11-0.46)], and/or treatment interruption due to adverse reactions [OR 0.23 (0.08-0.67)] decreased the chance of cure. Predictors of default, that is, use of noninjecting drugs [OR 3.00 (95% CL 1.31-6.88)], treatment interruption due to adverse reactions [OR 6.30 (1.81-21.95)], low schooling [OR 2.59 (2.15-5.82)], higher age [OR 0.44 (0.23-0.82)], and female gender [OR 0.28 (0.11-0.71)], reduced the chance of treatment default. Tuberculosis diagnosis based on sputum smear [OR 7.77 (1.94-31.09)] and/or arterial hypertension [OR 4.07 (1.25-13.18)] was associated with treatment failure. Conclusion. Mortality and default were low considering the prevalence of HIV infection; however cure was not significantly increased.

Precaução de contato: percepção dos acompanhantes de crianças internadas em unidade pediátrica / Contact precaution: the perception of people accompanying children hospitalized at a pediatric unit

Trata-se de uma pesquisa de campo, descritiva e exploratória de abordagem qualitativa, realizada na unidade pediátrica de um hospital universitário do Norte do Paraná, cujo objetivo foi analisar a percepção do acompanhante quanto à precaução de contato. Participaram vinte acompanhantes e o instrumento para coleta de dados foi composto por duas partes: a primeira destinada à obtenção de dados sociais do acompanhante e a segunda a questões norteadoras sobre a temática. Após a análise dos dados, em que se utilizou o método de interpretação dos sentidos composto por três etapas distintas, emergiram quatro categorias: "Orientações sobre a precaução de contato aos acompanhantes"; "Entendimento sobre a utilidade da precaução de contato"; "Dificuldades e facilidades na utilização da precaução de contato" e "Sentimentos em relação à vivência". A maioria demonstrou não entender a utilidade da prática e as dificuldades maiores foram relacionadas ao desconforto físico e mudança na rotina. Sentimentos como constrangimento, preconceito e humilhação foram associados à vivência. Há necessidade de aperfeiçoamento das informações fornecidas, melhor supervisão da utilização correta da paramentação e suporte emocional para as acompanhantes pelos profissionais de saúde.

This is a descriptive, exploratory and qualitative fieldwork conducted at the pediatric unit of a university hospital in northern Paraná. The purpose was to analyze the perception of people accompanying hospitalized children in regards to contact precaution. Twenty individuals participated and the instrument used for data collection had two parts: the first part was directed at obtaining the accompanying person ́s social data; and the second one contained guiding questions on the topic. After analyzing the data in which the method of interpretation of the senses was used, consisting of three distinct steps, four categories emerged: "Instructions about contact precautions to accompanying persons"; "Understanding the usefulness of contact precautions"; "Difficulties and easy aspects of using contact precautions" and "Feelings in relation to the experience". The majority demonstrated that they did not understand the usefulness of this practice, and the main difficulties were related to physical discomfort and changes in routine. Feelings such as embarrassment, humiliation and prejudice were associated with experience. It is necessary to improve the information provided, regarding the correct use of apparel, and the emotional support offered to accompanying persons by health professionals.